Articoli di riviste: "CD1 proteins"

1

Huang, Shouxiong, Tan-Yun Cheng, John Altman e D. Branch Moody. "Comparative lipidomics reveals a global sampling of major cellular membrane lipids by human CD1 proteins (P5006)". Journal of Immunology 190, n. 1_Supplement (1 maggio 2013): 41.4. http://dx.doi.org/10.4049/jimmunol.190.supp.41.4.

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Abstract Human CD1 proteins have differentially shaped grooves and present bacterial or self lipid antigens to T cells, but it is unknown whether the pool of endogenous lipids are differently sampled by each type of CD1 proteins. We used recently established lipidomic approach to analyze the molecules extracted from human CD1a, CD1b, CD1c, and CD1d proteins. In the study, we demonstrated that this highly sensitive and accurate lipidomic approach detected more than one thousand diverse molecules defined by accurate mass retention time values, which represented hundreds of lipid species associated with CD1 proteins. More than fifty percent of these molecules were shared by all four types of CD1 proteins and additional thirty percent shared by two or three CD1 isoforms. Further mass spectrometry analyses of collision-induced dissociation showed that the molecules eluted from all four types of CD1 proteins mainly are lipids from subcellular membranes, including phospholipids of conventional, ether-linked, and lyso forms and sphingolipids. Surprisingly, CD1 isoforms with bigger grooves preferred to lipids with shorter chains, which can be explained by small spacer or scaffold lipids that bind together with antigens. Whereas previous studies argued that one lipid molecule blocks CD1 grooves, analogous to MHC class II-associated CLIP peptide, we conclude that CD1 proteins broadly sample cellular lipids and two small lipids are able to be adapted into a big groove.

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Huang, Shouxiong, Tan-Yun Cheng, David Young, Emilie Layre, Cressida Madigan, John Shires, Vincenzo Cerundolo, John Altman e Branch Moody. "A CD1 lipidomic analysis determines the structures of human CD1b scaffold lipids and its function to enhance mycobacterial antigen presentation (106.43)". Journal of Immunology 188, n. 1_Supplement (1 maggio 2012): 106.43. http://dx.doi.org/10.4049/jimmunol.188.supp.106.43.

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Abstract Unlike the dominant role of one class II invariant chain peptide (CLIP) in blocking MHC class II, comparative lipidomics analysis shows that human CD1a, CD1b, CD1c and CD1d proteins bind lipids corresponding to hundreds of diverse accurate mass retention time values. Although most ions were observed in association with several CD1 proteins, ligands binding selectively to one CD1 isoform allowed the study of how differing antigen binding grooves influence lipid capture. The CD1b groove is distinguished by its unusually large volume, however, the average mass of compounds eluted from CD1b was similar to that of lipids from other CD1 proteins. Elution of small ligands from the large CD1b groove might be explained, if two small lipids bind simultaneously in the groove. In the context of the known CD1b crystal structures with scaffold lipids seated below the antigen, we also found that ligands selectively associated with CD1b lacked the hydrophilic head group, which is generally needed for antigen recognition, but interferes with scaffold function. Furthermore, we identified the scaffolds as deoxyceramides and diacylglycerols and directly demonstrated a function in augmenting presentation of a mycobacterial antigen, the short chain glucose monomycolate, to T cells. Thus, unlike MHC class II, CD1 proteins capture highly diverse ligands in the secretory pathway. CD1b has a mechanism for binding two small lipids to enhance bacterial antigen presentation and T cell activation.

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Aruffo, A., e B. Seed. "Expression of cDNA clones encoding the thymocyte antigens CD1a, b, c demonstrates a hierarchy of exclusion in fibroblasts." Journal of Immunology 143, n. 5 (1 settembre 1989): 1723–30. http://dx.doi.org/10.4049/jimmunol.143.5.1723.

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Abstract The CD1 gene family encodes at least three proteins: CD1a, CD1b, and CD1c, which are coexpressed on cortical thymocytes and a number of T cell leukemias. On thymocytes, CD1a forms noncovalent complexes with CD1b and CD1c, and a disulfide-linked heterodimer with CD8. This report describes the isolation and characterization of cDNA clones encoding the CD1a, CD1b, and CD1c Ag. Cotransfection of the cDNA was used to investigate the formation of intermolecular heterodimers by CD1a with other members of the CD1 gene family and with CD8. No intermolecular heterodimers were observed during transient expression in COS cells. However, an exclusion hierarchy was observed between members of the CD1 gene family when two or more members of the family were cotransfected into COS cells.

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Moody, D. Branch, e Sara Suliman. "CD1: From Molecules to Diseases". F1000Research 6 (30 ottobre 2017): 1909. http://dx.doi.org/10.12688/f1000research.12178.1.

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The human cluster of differentiation (CD)1 system for antigen display is comprised of four types of antigen-presenting molecules, each with a distinct functional niche: CD1a, CD1b, CD1c, and CD1d. Whereas CD1 proteins were thought solely to influence T-cell responses through display of amphipathic lipids, recent studies emphasize the role of direct contacts between the T-cell receptor and CD1 itself. Moving from molecules to diseases, new research approaches emphasize human CD1-transgenic mouse models and the study of human polyclonal T cells in vivo or ex vivo in disease states. Whereas the high genetic diversity of major histocompatibility complex (MHC)-encoded antigen-presenting molecules provides a major hurdle for designing antigens that activate T cells in all humans, the simple population genetics of the CD1 system offers the prospect of discovering or designing broadly acting immunomodulatory agents.

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Dascher, Christopher C., Kenji Hiromatsu, Jerome W. Naylor, Pamela P. Brauer, Kara A. Brown, James R. Storey, Samuel M. Behar et al. "Conservation of a CD1 Multigene Family in the Guinea Pig". Journal of Immunology 163, n. 10 (15 novembre 1999): 5478–88. http://dx.doi.org/10.4049/jimmunol.163.10.5478.

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Abstract CD1 is a family of cell-surface molecules capable of presenting microbial lipid Ags to specific T cells. Here we describe the CD1 gene family of the guinea pig (Cavia porcellus). Eight distinct cDNA clones corresponding to CD1 transcripts were isolated from a guinea pig thymocyte cDNA library and completely sequenced. The guinea pig CD1 proteins predicted by translation of the cDNAs included four that can be classified as homologues of human CD1b, three that were homologues of human CD1c, and a single CD1e homologue. These guinea pig CD1 protein sequences contain conserved amino acid residues and hydrophobic domains within the putative Ag binding pocket. A mAb specific for human CD1b cross-reacted with multiple guinea pig CD1 isoforms, thus allowing direct analysis of the structure and expression of at least a subset of guinea pig CD1 proteins. Cell-surface expression of CD1 was detected on cortical thymocytes, dermal dendritic cells in the skin, follicular dendritic cells of lymph nodes, and in the B cell regions within the lymph nodes and spleen. CD1 proteins were also detected on a subset of PBMCs consistent with expression on circulating B cells. This distribution of CD1 staining in guinea pig tissues was thus similar to that seen in other mammals. These data provide the foundation for the development of the guinea pig as an animal model to study the in vivo function of CD1.

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Faraldo-Gómez, José D., e Diana Garzón. "Molecular modeling and simulation studies of CD1 binding proteins (78.3)". Journal of Immunology 182, n. 1_Supplement (1 aprile 2009): 78.3. http://dx.doi.org/10.4049/jimmunol.182.supp.78.3.

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Abstract The presentation of small protein fragments, both foreign and native, on the surface of specialized cells is one of the cornerstones of our immune system. In complex with MHC binding proteins, these protein antigens will be recognized by T-cell membrane receptors either as self or non-self, and an appropriate response will be initiated. In recent years it has become apparent that immune responses may also be induced by a diverse array of lipid antigens. The presentation of these antigens involves a class of binding proteins referred to as CD1, analogous to MHC proteins. The CD1 family includes 5 isoforms of distinct specificity, of which CD1a, CD1b and CD1d have been characterized structurally in complex with diverse lipid antigens. Here we report the results of extensive computer simulation studies of this family, from which we gain insights into the mechanism of lipid binding. We also present a molecular model of CD1c, and based on this, rationalize its specificity for branched mycobacterial lipids.

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Gherardin, Nicholas A., Samuel J. Redmond, Hamish E. G. McWilliam, Catarina F. Almeida, Katherine H. A. Gourley, Rebecca Seneviratna, Shihan Li et al. "CD36 family members are TCR-independent ligands for CD1 antigen–presenting molecules". Science Immunology 6, n. 60 (25 giugno 2021): eabg4176. http://dx.doi.org/10.1126/sciimmunol.abg4176.

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CD1c presents lipid-based antigens to CD1c-restricted T cells, which are thought to be a major component of the human T cell pool. However, the study of CD1c-restricted T cells is hampered by the presence of an abundantly expressed, non–T cell receptor (TCR) ligand for CD1c on blood cells, confounding analysis of TCR-mediated CD1c tetramer staining. Here, we identified the CD36 family (CD36, SR-B1, and LIMP-2) as ligands for CD1c, CD1b, and CD1d proteins and showed that CD36 is the receptor responsible for non–TCR-mediated CD1c tetramer staining of blood cells. Moreover, CD36 blockade clarified tetramer-based identification of CD1c-restricted T cells and improved identification of CD1b- and CD1d-restricted T cells. We used this technique to characterize CD1c-restricted T cells ex vivo and showed diverse phenotypic features, TCR repertoire, and antigen-specific subsets. Accordingly, this work will enable further studies into the biology of CD1 and human CD1-restricted T cells.

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Cheng, Janice M. H., Ashna A. Khan, Mattie S. M. Timmer e Bridget L. Stocker. "Endogenous and Exogenous CD1-Binding Glycolipids". International Journal of Carbohydrate Chemistry 2011 (5 aprile 2011): 1–13. http://dx.doi.org/10.1155/2011/749591.

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In the same way that peptide antigens are presented by major histocompatibility complex (MHC) molecules, glycolipid antigens can also activate the immune response via binding to CD1 proteins on antigen-presenting cells (APCs) and stimulate CD1-restricted T cells. In humans, there are five members of the CD1 family, termed CD1a–e, of which CD1a–d are involved in glycolipid presentation at the cell surface, while CD1e is involved in the intracellular trafficking of glycolipid antigens. Both endogenous (self-derived) and exogenous (non-self-derived) glycolipids have been shown to bind to members of the CD1 family with varying degrees of specificity. In this paper we focus on the key glycolipids that bind to the different members of the CD1 family.

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Li, Sha, Hak-Jong Choi, Sharmila Shanmuganad e Chyung-Ru Wang. "Phenotypic and functional characterization of group 1 CD1-restricted autoreactive T cells in a transgenic mouse model expressing human group 1 CD1 and a CD1b-specific T cell receptor (36.31)". Journal of Immunology 184, n. 1_Supplement (1 aprile 2010): 36.31. http://dx.doi.org/10.4049/jimmunol.184.supp.36.31.

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Abstract Unlike other MHC molecules, the CD1 family presents self and foreign lipid antigens to multiple T cell subsets. In humans, this family consists of group 1 CD1 molecules CD1a, b and c and group 2 molecule CD1d. While CD1d-restricted NKT cells have been well-studied, our knowledge of the development and function of group 1 CD1-restricted T cells has been limited by the lack of a suitable animal model. We have generated double transgenic mice (hCD1Tg/HJ1Tg) that express the human group 1 CD1 proteins in a pattern similar to that observed in humans in addition to a TCR from a CD1b-restricted autoreactive T cell clone. Like NKT cells, the majority of HJ1Tg T cells that develop in hCD1Tg/HJ1Tg mice express NK markers and exhibit an activated phenotype. In addition, HJ1Tg T cells are highly enriched in the liver. The development of HJ1Tg T cells with the NKT cell phenotype is group 1 CD1-dependent, as NK1.1+ HJ1Tg T cells are absent in HJ1Tg mice that lack the human group 1 CD1 genes. Upon stimulation with group 1 CD1-expressing dendritic cells, HJ1Tg T cells primarily secrete proinflammatory cytokines, including IFN-γ, IL-17A, IL-6 and MCP-1. These cytokine productions can be further enhanced in the presence of TLR agonists, a phenomenon also observed in autoreactive NKT cells. The similarities between the phenotype and functional properties of HJ1Tg T cells and NKT cells suggest that these two autoreactive T cell subsets may play similar immunological roles.

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Gadola, Stephan D., Anastasios Karadimitris, Nathan R. Zaccai, Mariolina Salio, Nicolas Dulphy, Dawn Shepherd, E. Yvonne Jones e Vincenzo Cerundolo. "Generation of CD1 tetramers as a tool to monitor glycolipid–specific T cells". Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 358, n. 1433 (29 maggio 2003): 875–77. http://dx.doi.org/10.1098/rstb.2003.1267.

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CD1 molecules are β 2 m–associated HLA class–I–like glycoproteins which have the unique ability to present glycolipid and phospholipid antigens to specific T lymphocytes. To study the biology of CD1 and its role in human disease we developed novel techniques for generation of recombinant CD1/lipid complexes by in vitro refolding. Fluorescent tetrameric complexes made from soluble recombinant CD1d/α–galactosylceramide complexes allowed highly sensitive and specific ex vivo and in vitro detection and functional characterization of novel human T–lymphocyte populations. Furthermore, protein crystals were obtained from soluble recombinant CD1b/β 2 m–proteins loaded either with phosphatidylinositol or ganglioside GM2, which led to the first atomic structure determination of a CD1/lipid complex. The analysis of these crystal structures clarified how CD1b molecules can bind lipid ligands of different size, and revealed a broader spectrum of potential CD1b ligands than previously predicted.

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Van Rhijn, Ildiko, David C. Young, Annemieke De Jong, Jenny Vazquez, Tan-Yun Cheng, Rahul Talekar, Duarte C. Barral et al. "CD1c bypasses lysosomes to present a lipopeptide antigen with 12 amino acids". Journal of Experimental Medicine 206, n. 6 (25 maggio 2009): 1409–22. http://dx.doi.org/10.1084/jem.20082480.

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The recent discovery of dideoxymycobactin (DDM) as a ligand for CD1a demonstrates how a nonribosomal lipopeptide antigen is presented to T cells. DDM contains an unusual acylation motif and a peptide sequence present only in mycobacteria, but its discovery raises the possibility that ribosomally produced viral or mammalian proteins that commonly undergo lipidation might also function as antigens. To test this, we measured T cell responses to synthetic acylpeptides that mimic lipoproteins produced by cells and viruses. CD1c presented an N-acyl glycine dodecamer peptide (lipo-12) to human T cells, and the response was specific for the acyl linkage as well as the peptide length and sequence. Thus, CD1c represents the second member of the CD1 family to present lipopeptides. lipo-12 was efficiently recognized when presented by intact cells, and unlike DDM, it was inactivated by proteases and augmented by protease inhibitors. Although lysosomes often promote antigen presentation by CD1, rerouting CD1c to lysosomes by mutating CD1 tail sequences caused reduction in lipo-12 presentation. Thus, although certain antigens require antigen processing in lysosomes, others are destroyed there, providing a hypothesis for the evolutionary conservation of large CD1 families containing isoforms that survey early endosomal pathways.

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Beckman, E. M., A. Melián, S. M. Behar, P. A. Sieling, D. Chatterjee, S. T. Furlong, R. Matsumoto, J. P. Rosat, R. L. Modlin e S. A. Porcelli. "CD1c restricts responses of mycobacteria-specific T cells. Evidence for antigen presentation by a second member of the human CD1 family." Journal of Immunology 157, n. 7 (1 ottobre 1996): 2795–803. http://dx.doi.org/10.4049/jimmunol.157.7.2795.

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Abstract Previous studies suggest that CD1 is a family of Ag-presenting molecules distantly related to those encoded by the MHC. However, of the four known human CD1 proteins, only CD1b has been shown to restrict Ag-specific T cell responses. In this study, we have shown that a second member of the human CD1 family, CD1c, could also mediate Ag presentation to T cells. Three T cell lines recognizing mycobacterial Ags in a CD1c-restricted manner were isolated from normal donor blood. These T cells were MHC unrestricted, and their recognition of Ag was independent of the products of the transporter associated with Ag presentation-1/2 and DMA/B genes that are generally required for Ag presentation by MHC-encoded Ag-presenting molecules. Furthermore, unlike MHC-restricted responses to peptides, the CD1c-restricted T cell lines recognized protease-resistant mycobacterial lipid Ags. These T cell lines also showed significant cytotoxicity toward CD1c-expressing target cells even in the absence of mycobacterial Ags, which was shown by clonal analysis to be mediated by a subpopulation of T cells directly reactive to CD1c molecules. Our findings establish the ability of a second member of the CD1 family to restrict responses of Ag-specific T cells, and thus support the general hypothesis that the CD1 family comprises a third lineage of Ag-presenting molecules that presents a novel class of foreign and self Ags to MHC-unrestricted T cells.

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Shamin, Maria, Tomasz H. Benedyk, Stephen C. Graham e Janet E. Deane. "The lipid transfer protein Saposin B does not directly bind CD1d for lipid antigen loading". Wellcome Open Research 4 (2 agosto 2019): 117. http://dx.doi.org/10.12688/wellcomeopenres.15368.1.

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Background: Lipid antigens are presented on the surface of cells by the CD1 family of glycoproteins, which have structural and functional similarity to MHC class I molecules. The hydrophobic lipid antigens are embedded in membranes and inaccessible to the lumenal lipid-binding domain of CD1 molecules. Therefore, CD1 molecules require lipid transfer proteins for lipid loading and editing. CD1d is loaded with lipids in late endocytic compartments, and lipid transfer proteins of the saposin family have been shown to play a crucial role in this process. However, the mechanism by which saposins facilitate lipid binding to CD1 molecules is not known and is thought to involve transient interactions between protein components to ensure CD1-lipid complexes can be efficiently trafficked to the plasma membrane for antigen presentation. Of the four saposin proteins, the importance of Saposin B (SapB) for loading of CD1d is the most well-characterised. However, a direct interaction between CD1d and SapB has yet to be described. Methods: In order to determine how SapB might load lipids onto CD1d, we used purified, recombinant CD1d and SapB and carried out a series of highly sensitive binding assays to monitor direct interactions. We performed equilibrium binding analysis, chemical cross-linking and co-crystallisation experiments, under a range of different conditions. Results: We could not demonstrate a direct interaction between SapB and CD1d using any of these binding assays. Conclusions: This work establishes comprehensively that the role of SapB in lipid loading does not involve direct binding to CD1d. We discuss the implication of this for our understanding of lipid loading of CD1d and propose several factors that may influence this process.

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Shamin, Maria, Tomasz H. Benedyk, Stephen C. Graham e Janet E. Deane. "The lipid transfer protein Saposin B does not directly bind CD1d for lipid antigen loading". Wellcome Open Research 4 (18 ottobre 2019): 117. http://dx.doi.org/10.12688/wellcomeopenres.15368.2.

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Background: Lipid antigens are presented on the surface of cells by the CD1 family of glycoproteins, which have structural and functional similarity to MHC class I molecules. The hydrophobic lipid antigens are embedded in membranes and inaccessible to the lumenal lipid-binding domain of CD1 molecules. Therefore, CD1 molecules require lipid transfer proteins for lipid loading and editing. CD1d is loaded with lipids in late endocytic compartments, and lipid transfer proteins of the saposin family have been shown to play a crucial role in this process. However, the mechanism by which saposins facilitate lipid binding to CD1 molecules is not known and is thought to involve transient interactions between protein components to ensure CD1-lipid complexes can be efficiently trafficked to the plasma membrane for antigen presentation. Of the four saposin proteins, the importance of Saposin B (SapB) for loading of CD1d is the most well-characterised. However, a direct interaction between CD1d and SapB has yet to be described. Methods: In order to determine how SapB might load lipids onto CD1d, we used purified, recombinant CD1d and SapB and carried out a series of highly sensitive binding assays to monitor direct interactions. We performed equilibrium binding analysis, chemical cross-linking and co-crystallisation experiments, under a range of different conditions. Results: We could not demonstrate a direct interaction between SapB and CD1d using any of these binding assays. Conclusions: This work strongly indicates that the role of SapB in lipid loading does not involve direct binding to CD1d. We discuss the implication of this for our understanding of lipid loading of CD1d and propose several factors that may influence this process.

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Campana, D., G. Janossy, E. Coustan-Smith, P. L. Amlot, W. T. Tian, S. Ip e L. Wong. "The expression of T cell receptor-associated proteins during T cell ontogeny in man." Journal of Immunology 142, n. 1 (1 gennaio 1989): 57–66. http://dx.doi.org/10.4049/jimmunol.142.1.57.

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Abstract The expression of TCR-associated molecules was examined in human fetal and postnatal tissues. From gestational wk 7 onward in the fetal liver, putative prothymocytes have been identified with cytoplasmic CD3 positivity (cCD3+). These immature cells are TdT- and do not express membrane CD3 (mCD3-) or TCR beta identified by beta F1, but show CD7 and CD45 positivity without CD1, CD2, CD5, CD4, CD8, CD10, and class II Ag. Their high proliferative activity is indicated by greater than 85% Ki67 positivity. After the 10th wk, beta F1+, mCD3+ cells also appear in the liver and these are mostly Ki67- but no TCR gamma delta-bearing cells can be identified at such an early stage of extrathymic development. In the mCD3- TdT-fetal thymus (10 1/2 to 18th wk) cCD3+, mCD3- CD1-blasts proliferate (Ki67+) and lack TCR-beta or TCR-gamma delta. The TdT-, CD1+ cortical thymocytes develop into TCR-beta + and WT31-positive (TCR-alpha beta +) cells. Subsequently TdT-positive thymocytes become detectable around 19 to 20 wk, and in such glands the peak of proliferative activity is seen among TdT+, cCD3+ cells which appear to acquire, in a regular sequence, cytoplasmic beta F1 (TCR-beta), mCD3, and TCR-alpha beta (WT31 positivity) together with the loss of TdT and Ki67 positivity. A newly described transitional population of cells is TdT-, beta F1+ but exhibits no detectable WT31 positivity. These cells correspond to the CD1+, mCD3+ thymocytes and are probably the targets of thymic selection. The cells of the TCR-gamma delta lineage, detected by mAb TCR-delta-1 and delta TCS1, are rare (0.02 to 0.5%) among thymocytes from gestational wk 10 1/2 onward through the whole span of thymic development, but these cells include a proportion (18 to 59%) of cells expressing CD1 Ag, suggesting that these TCR-gamma delta cells differentiate in the thymus. Among the CD1+, TCR-gamma delta + thymocytes, no TdT positivity can be detected.

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Sieling, Peter A., Denis Jullien, Monica Dahlem, Thomas F. Tedder, Thomas H. Rea, Robert L. Modlin e Steven A. Porcelli. "CD1 Expression by Dendritic Cells in Human Leprosy Lesions: Correlation with Effective Host Immunity". Journal of Immunology 162, n. 3 (1 febbraio 1999): 1851–58. http://dx.doi.org/10.4049/jimmunol.162.3.1851.

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Abstract A potential role for the CD1 family of lipid Ag-presenting molecules in antimicrobial immunity in vivo was investigated in human leprosy skin lesions. Strong induction of three CD1 proteins (CD1a, -b, and -c) was observed in dermal granulomas in biopsy samples of involved skin from patients with the tuberculoid form of leprosy or with reversal reactions, which represent clinical patterns of disease associated with active cellular immunity to Mycobacterium leprae. In contrast, lesions from patients with the lepromatous form of the disease who lack effective cell-mediated immunity to the pathogen did not show induction of CD1 proteins. Thus, expression of CD1 correlated directly with effective immunity to M. leprae, as assessed by the clinical course of infection. CD1a, -b, and -c could be induced to similar levels on monocytes from the blood of either tuberculoid or lepromatous leprosy patients. This suggested that the absence of expression in lepromatous lesions was most likely due to local factors at the site of infection as opposed to a primary defect of the CD1 system itself. The majority of cells expressing CD1 in leprosy lesions were identified as a population of CD83+ dendritic cells. Initial in vitro studies of the Ag-presenting function of CD1+CD83+ monocyte-derived dendritic cells showed that such cells were highly efficient APCs for CD1-restricted T cells. These results indicate that the CD1 system can be up-regulated in human infectious diseases in vivo, and may play a role in augmenting host defense against microbial pathogens.

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Sun, Xiao-Meng, Zhao Xue, Mei-Ling Sun, Yi Zhang, Yu-Zhong Zhang, Hui-Hui Fu, Yu-Qiang Zhang e Peng Wang. "Characterization of a Novel Alginate Lyase with Two Alginate Lyase Domains from the Marine Bacterium Vibrio sp. C42". Marine Drugs 20, n. 12 (26 novembre 2022): 746. http://dx.doi.org/10.3390/md20120746.

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Alginate is abundant in the cell walls of brown algae. Alginate lyases can degrade alginate, and thus play an important role in the marine carbon cycle and industrial production. Currently, most reported alginate lyases contain only one functional alginate lyase domain. AlyC8 is a putative alginate lyase with two alginate lyase domains (CD1 and CD2) from the marine alginate-degrading strain Vibrio sp. C42. To characterize AlyC8 and its two catalytic domains, AlyC8 and its two catalytic domain-deleted mutants, AlyC8-CD1 and AlyC8-CD2, were expressed in Escherichia coli. All three proteins have noticeable activity toward sodium alginate and exhibit optimal activities at pH 8.0–9.0 and at 30–40 °C, demonstrating that both CD1 and CD2 are functional. However, CD1 and CD2 showed opposite substrate specificity. The differences in substrate specificity and degradation products of alginate between the mutants and AlyC8 demonstrate that CD1 and CD2 can act synergistically to enable AlyC8 to degrade various alginate substrates into smaller oligomeric products. Moreover, kinetic analysis indicated that AlyC8-CD1 plays a major role in the degradation of alginate by AlyC8. These results demonstrate that AlyC8 is a novel alginate lyase with two functional catalytic domains that are synergistic in alginate degradation, which is helpful for a better understanding of alginate lyases and alginate degradation.

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Cuevas-Zuviría, Bruno, Marina Mínguez-Toral, Araceli Díaz-Perales, María Garrido-Arandia e Luis F. Pacios. "Structural Dynamics of the Lipid Antigen-Binding Site of CD1d Protein". Biomolecules 10, n. 4 (1 aprile 2020): 532. http://dx.doi.org/10.3390/biom10040532.

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CD1 molecules present lipid antigens to T-cells in early stages of immune responses. Whereas CD1‒lipid‒T-cell receptors interactions are reasonably understood, molecular details on initial trafficking and loading of lipids onto CD1 proteins are less complete. We present a molecular dynamics (MD) study of human CD1d, the isotype that activates iNKT cells. MD simulations and calculations of properties and Poisson-Boltzmann electrostatic potentials were used to explore the dynamics of the antigen-binding domain of the apo-form, CD1d complexes with three lipid–antigens that activate iNKT cells and CD1d complex with GM2AP, a protein that assists lipid loading onto CD1 molecules in endosomes/lysosomes. The study was done at pH 7 and 4.5, values representative of strongly acidic environments in endosomal compartments. Our findings revealed dynamic features of the entrance to the hydrophobic channels of CD1d modulated by two α helices with sensitivity to the type of lipid. We also found lipid- and pH-dependent dynamic changes in three exposed tryptophans unique to CD1d among the five human CD1 isotypes. On the basis of modelled structures, our data also revealed external effects produced by the helper protein GM2AP only when it interacts in its open form, thus suggesting that the own assistant protein also adapts conformation to association with CD1d.

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Van Rhijn, Ildiko, Ad P. Koets, Jin Seon Im, Diewertje Piebes, Faye Reddington, Gurdyal S. Besra, Steven A. Porcelli, Willem van Eden e Victor P. M. G. Rutten. "The Bovine CD1 Family Contains Group 1 CD1 Proteins, but No Functional CD1d". Journal of Immunology 176, n. 8 (3 aprile 2006): 4888–93. http://dx.doi.org/10.4049/jimmunol.176.8.4888.

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Bourgeois, Elvire A., Sumithra Subramaniam, Tan-Yun Cheng, Annemieke De Jong, Emilie Layre, Dalam Ly, Maryam Salimi et al. "Bee venom processes human skin lipids for presentation by CD1a". Journal of Experimental Medicine 212, n. 2 (12 gennaio 2015): 149–63. http://dx.doi.org/10.1084/jem.20141505.

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Venoms frequently co-opt host immune responses, so study of their mode of action can provide insight into novel inflammatory pathways. Using bee and wasp venom responses as a model system, we investigated whether venoms contain CD1-presented antigens. Here, we show that venoms activate human T cells via CD1a proteins. Whereas CD1 proteins typically present lipids, chromatographic separation of venoms unexpectedly showed that stimulatory factors partition into protein-containing fractions. This finding was explained by demonstrating that bee venom–derived phospholipase A2 (PLA2) activates T cells through generation of small neoantigens, such as free fatty acids and lysophospholipids, from common phosphodiacylglycerides. Patient studies showed that injected PLA2 generates lysophospholipids within human skin in vivo, and polyclonal T cell responses are dependent on CD1a protein and PLA2. These findings support a previously unknown skin immune response based on T cell recognition of CD1a proteins and lipid neoantigen generated in vivo by phospholipases. The findings have implications for skin barrier sensing by T cells and mechanisms underlying phospholipase-dependent inflammatory skin disease.

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Hopkins, J., B. M. Dutia e S. M. Rhind. "Sheep CD1 genes and proteins". Veterinary Immunology and Immunopathology 73, n. 1 (gennaio 2000): 3–14. http://dx.doi.org/10.1016/s0165-2427(99)00159-2.

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22

Sundararaj, Srinivasan, Jingjing Zhang, S. Harsha Krovi, Romain Bedel, Kathryn D. Tuttle, Natacha Veerapen, Gurdyal S. Besra et al. "Differing roles of CD1d2 and CD1d1 proteins in type I natural killer T cell development and function". Proceedings of the National Academy of Sciences 115, n. 6 (19 gennaio 2018): E1204—E1213. http://dx.doi.org/10.1073/pnas.1716669115.

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Abstract (sommario):

MHC class I-like CD1 molecules have evolved to present lipid-based antigens to T cells. Differences in the antigen-binding clefts of the CD1 family members determine the conformation and size of the lipids that are presented, although the factors that shape CD1 diversity remain unclear. In mice, two homologous genes, CD1D1 and CD1D2, encode the CD1d protein, which is essential to the development and function of natural killer T (NKT) cells. However, it remains unclear whether both CD1d isoforms are equivalent in their antigen presentation capacity and functions. Here, we report that CD1d2 molecules are expressed in the thymus of some mouse strains, where they select functional type I NKT cells. Intriguingly, the T cell antigen receptor repertoire and phenotype of CD1d2-selected type I NKT cells in CD1D1−/− mice differed from CD1d1-selected type I NKT cells. The structures of CD1d2 in complex with endogenous lipids and a truncated acyl-chain analog of α-galactosylceramide revealed that its A′-pocket was restricted in size compared with CD1d1. Accordingly, CD1d2 molecules could not present glycolipid antigens with long acyl chains efficiently, favoring the presentation of short acyl chain antigens. These results indicate that the two CD1d molecules present different sets of self-antigen(s) in the mouse thymus, thereby impacting the development of invariant NKT cells.

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23

Guo, Tingxi, Edward M. Y. Koo e Naoto Hirano. "A Subset of Human Autoreactive CD1c-Restricted T Cells Preferentially Express TRBV4-1+ TCRs and Recognize Phospholipids". Journal of Immunology 198, n. 1_Supplement (1 maggio 2017): 52.6. http://dx.doi.org/10.4049/jimmunol.198.supp.52.6.

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Abstract (sommario):

Abstract Unlike the highly polymorphic, peptide-presenting conventional MHC molecules, CD1 consists of a family of monomorphic, lipid-presenting proteins. Recent studies have revealed the molecular basis of mycobacterial lipid recognition by CD1a-c-restricted T cells. In addition to foreign lipids, subsets of CD1a-c-restricted T cells recognize self-lipids, which may have implications for human diseases such as autoimmunity and cancer. And yet, the molecular identity of these self-reactive T cells remains largely elusive. In this study, using a novel CD1c+ artificial antigen-presenting cell (aAPC)-based system, we have isolated human CD1c-restricted autoreactive T cells and characterized them at the molecular level. By employing the human cell line K562, deficient in MHC class I/II and CD1 expression, as a backbone, we generated an aAPC expressing CD1c as the sole antigen-presenting molecule with costimulatory molecules, CD80 and CD83. When stimulated with this CD1c+ aAPC endogenously presenting self-lipids, a subpopulation of primary human CD4+ T cells from multiple donors consistently upregulated CD154 (CD40L) in a CD1c-specific manner. These activated CD4+ T cells preferentially expressed TRBV4-1+ TCRs. Interestingly, TRAV usage and CDR3 sequences of these TRBV4-1+ T cells were diverse. Clonotypic analyses of the reconstituted TRBV4-1+ TCRs demonstrated that the heterogeneity of the CDR3 sequences greatly impacted the strength of CD1c-restricted autoreactivity. Furthermore, cell-free assays using recombinant CD1c loaded with distinct lipids identified several phospholipid species as potential self-ligands. These data provide new insights into the molecular identity of human autoreactive CD1c-restricted T cells.

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Huang, Shouxiong, Manju Sharma, Xiang Zhang, Shuangmin Zhang, Liang Niu, Shuk-mei Ho e Aimin Chen. "Lipophilic air pollutants inhibit endocytic lipid antigen presentation". Journal of Immunology 198, n. 1_Supplement (1 maggio 2017): 146.8. http://dx.doi.org/10.4049/jimmunol.198.supp.146.8.

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Abstract (sommario):

Abstract Air pollutants as non-heritable factors are recognized as triggers for various human inflammatory diseases, in which T cells are central in producing cytokines and determining disease outcomes. We postulated that lipid antigen presentation mediated by cluster of differentiation 1 (CD1) proteins for T cell activation is susceptible to lipophilic air pollutants. To test this notion, we determined whether common lipophilic pollutants benzo[a]pyrene and diesel exhaust particles impact on the activation of lipid-specific T cells. Our results demonstrated that the expression of CD1a and CD1d proteins, and the activation of CD1a- and CD1d-restricted T cells were sensitively inhibited by benzo[a]pyrene even at low concentrations detectable in exposed human populations. Similarly, diesel exhaust particles showed marginal inhibitory effect. Using transcriptomic profiling, we discovered that gene expression for regulating endocytic and lipid metabolic pathways was perturbed by benzo[a]pyrene. Imaging flow cytometry also showed that CD1a and CD1d proteins were respectively retained in early and late endosomal compartments, supporting an impaired endocytic lipid antigen presentation for T cell activation upon benzo[a]pyrene exposure. This work conceptually demonstrates that lipid antigen presentation for T cell activation is inhibited by lipophilic pollutants through profound interference with gene expression and endocytic function, likely further disrupting regulatory cytokine secretion and ultimately exacerbating inflammatory diseases.

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25

Exley, Mark, Jorge Garcia, Steven P. Balk e Steven Porcelli. "Requirements for CD1d Recognition by Human Invariant Vα24+ CD4−CD8− T Cells". Journal of Experimental Medicine 186, n. 1 (7 luglio 1997): 109–20. http://dx.doi.org/10.1084/jem.186.1.109.

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Abstract (sommario):

A subset of human CD4−CD8− T cells that expresses an invariant Vα24-JαQ T cell receptor (TCR)-α chain, paired predominantly with Vβ11, has been identified. A series of these Vα24 Vβ11 clones were shown to have TCR-β CDR3 diversity and express the natural killer (NK) locus–encoded C-type lectins NKR-P1A, CD94, and CD69. However, in contrast to NK cells, they did not express killer inhibitory receptors, CD16, CD56, or CD57. All invariant Vα24+ clones recognized the MHC class I–like CD16 molecule and discriminated between CD1d and other closely related human CD1 proteins, indicating that recognition was TCR-mediated. Recognition was not dependent upon an endosomal targeting motif in the cytoplasmic tail of CD1d. Upon activation by anti-CD3 or CD1d, the clones produced both Th1 and Th2 cytokines. These results demonstrate that human invariant Vα24+ CD4−CD8− T cells, and presumably the homologous murine NK1+ T cell population, are CD1d reactive and functionally distinct from NK cells. The conservation of this cell population and of the CD1d ligand across species indicates an important immunological function.

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26

Raftery, Martin J., Manuel Hitzler, Florian Winau, Thomas Giese, Bodo Plachter, Stefan H. E. Kaufmann e Günther Schönrich. "Inhibition of CD1 Antigen Presentation by Human Cytomegalovirus". Journal of Virology 82, n. 9 (20 febbraio 2008): 4308–19. http://dx.doi.org/10.1128/jvi.01447-07.

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Abstract (sommario):

ABSTRACT The betaherpesvirus human cytomegalovirus (HCMV) encodes several molecules that block antigen presentation by the major histocompatibility complex (MHC) proteins. Humans also possess one other family of antigen-presenting molecules, the CD1 family; however, the effect of HCMV on CD1 expression is unknown. The majority of CD1 molecules are classified on the basis of homology as group 1 CD1 and are present almost exclusively on professional antigen-presenting cells such as dendritic cells, which are a major target for HCMV infection and latency. We have determined that HCMV encodes multiple blocking strategies targeting group 1 CD1 molecules. CD1 transcription is strongly inhibited by the HCMV interleukin-10 homologue cmvIL-10. HCMV also blocks CD1 antigen presentation posttranscriptionally by the inhibition of CD1 localization to the cell surface. This function is not performed by a known HCMV MHC class I-blocking molecule and is substantially stronger than the blockage induced by herpes simplex virus type 1. Antigen presentation by CD1 is important for the development of the antiviral immune response and the generation of mature antigen-presenting cells. HCMV present in antigen-presenting cells thus blunts the immune response by the blockage of CD1 molecules.

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27

Suryadevara, Naveen Chandra, Amrendra Kumar, Paul Chimski, Karin Oh, Courtney Caster, Richard R. Truman, Liming Ren, Mike Criscitiello e Sebastian Joyce. "On The Evolutionary Origins Of Cd1d And The Type I, Semi-Invariant Natural Killer T Cells". Journal of Immunology 202, n. 1_Supplement (1 maggio 2019): 73.2. http://dx.doi.org/10.4049/jimmunol.202.supp.73.2.

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Abstract (sommario):

Abstract The evolutionary origins of CD1d molecules and the T cell receptors (TCR) that recognize them currently remain unknown. CD1d molecules control the functions of a specialized subset of lymphocytes called semi-invariant natural killer T (type I NKT) cells. Type I NKT cells recognize both the self and non-self agonist —α-galactosylceramide (αGC) and related glycolipids— when presented by CD1d molecules. NKT cells express an invariant TCR α-chain (iTCRα) resulting from the mouse Vα14 or human Vα24 to Jα18 rearrangement. iTCRα pairs with the mouse Vβ8 (Vβ7, Vβ6, Vβ2) or the orthologous human Vβ11 TCR β-chain to create a functional NKTCR. Our phylogenetic analyses revealed that whilst the mouse Cd1 homologs have Mesozoic origin in they they evolved as far back asin the anole lizards, the orthologues of Cd1d and that of Vα14/Vα24 and Jα18 gene segments emerged with the decent of mammals. Moreover, the known avian CD1 orthologs lack the α3 domain and both the reptilian and the avian CD1 lack a functional endo/lysosomal-recycling motif critical for NKT cell development and function. As well, monotreme genomes lack Cd1d, Vα14/Vα24 and Jα18 orthologs and the marsupial Cd1d, Vα14/Vα24 and Jα18 orthologs harbor indels that would render the encoded proteins non-functional. Consistent with these findings, one of the most divergent Cd1d gene isolated from the nine-banded armadillo Dasypus novemcinctus and ectopically expressed in a cell line presented αGC and activated mouse NKT cell hybridomas. Hence, we conclude that the CD1d-restricted αGC-presentation in the immune system evolved more recently as an eutherian innovation.

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28

Ward, Nicole L., Elizabeth Moore, Kristen Noon, Nicholas Spassil, Erica Keenan, Tammy L. Ivanco e Joseph C. LaManna. "Cerebral angiogenic factors, angiogenesis, and physiological response to chronic hypoxia differ among four commonly used mouse strains". Journal of Applied Physiology 102, n. 5 (maggio 2007): 1927–35. http://dx.doi.org/10.1152/japplphysiol.00909.2006.

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Abstract (sommario):

Angiogenesis is a critical element for adaptation to low levels of oxygen and occurs following long-term exposure to mild hypoxia in rats. To test whether a similar response in mice occurs, CD1, 129/Sv, C57Bl/6, and Balb/c mice were exposed to 10% oxygen for up to 3 wk. All mice showed significant increases in the percentage of packed red blood cells, and CD1 and 129/Sv mice showed increased respiration frequency and minute volume, common physiological measures of hypoxia. Significant angiogenesis was observed in all strains except Balb/c following 3-wk exposure to chronic hypoxia. CD1 hypoxic mice had the largest increase (88%), followed by C57Bl/6 (48%), 129/Sv (41%), and Balb/c (12%), suggesting that some mice undergo more remodeling than others in response to hypoxia. Protein expression analysis of vascular endothelial growth factor (VEGF), angiopoietin (Ang)-1 and Ang2, and Tie2 were examined to determine whether regulation of different angiogenic proteins could account for the differences observed in hypoxia-induced angiogenesis. CD1 mice showed the strongest upregulation of VEGF, Ang2, Ang1, and Tie2, whereas Balb/c had only subtle increases in VEGF and no change in the other proteins. C57Bl/6 mice showed a regulatory response that fell between the CD1 and Balb/c mice, consistent with the intermediate increase in angiogenesis. Our results suggest that genetic heterogeneity plays a role in angiogenesis and regulation of angiogenic proteins and needs to be accounted for when designing and interpreting experiments using transgenic mice and when studying in vivo models of angiogenesis.

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29

Shiratsuchi, Takayuki, Jonathan Schneck, Akira Kawamura e Moriya Tsuji. "Human CD1 dimeric proteins as indispensable tools for research on CD1-binding lipids and CD1-restricted T cells". Journal of Immunological Methods 345, n. 1-2 (giugno 2009): 49–59. http://dx.doi.org/10.1016/j.jim.2009.04.002.

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30

Zajonc, Dirk M., Harald Striegl, Christopher C. Dascher e Ian A. Wilson. "The crystal structure of avian CD1 reveals a smaller, more primordial antigen-binding pocket compared to mammalian CD1". Proceedings of the National Academy of Sciences 105, n. 46 (12 novembre 2008): 17925–30. http://dx.doi.org/10.1073/pnas.0809814105.

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Abstract (sommario):

The molecular details of glycolipid presentation by CD1 antigen-presenting molecules are well studied in mammalian systems. However, little is known about how these non-classical MHC class I (MHCI) molecules diverged from the MHC locus to create a more complex, hydrophobic binding groove that binds lipids rather than peptides. To address this fundamental question, we have determined the crystal structure of an avian CD1 (chCD1–2) that shares common ancestry with mammalian CD1 from ≈310 million years ago. The chCD1–2 antigen-binding site consists of a compact, narrow, central hydrophobic groove or pore rather than the more open, 2-pocket architecture observed in mammalian CD1s. Potential antigens then would be restricted in size to single-chain lipids or glycolipids. An endogenous ligand, possibly palmitic acid, serves to illuminate the mode and mechanism of ligand interaction with chCD1–2. The palmitate alkyl chain is inserted into the relatively shallow hydrophobic pore; its carboxyl group emerges at the receptor surface and is stabilized by electrostatic and hydrogen bond interactions with an arginine residue that is conserved in all known CD1 proteins. In addition, other novel features, such as an A′ loop that interrupts and segments the normally long, continuous α1 helix, are unique to chCD1–2 and contribute to the unusually narrow binding groove, thereby limiting its size. Because birds and mammals share a common ancestor, but the rate of evolution is slower in birds than in mammals, the chCD1–2-binding groove probably represents a more primordial CD1-binding groove.

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31

Hiromatsu, Kenji, Christopher C. Dascher, Masahiko Sugita, Cindy Gingrich-Baker, Samuel M. Behar, Kenneth P. LeClair, Michael B. Brenner e Steven A. Porcelli. "Characterization of guinea-pig group 1 CD1 proteins". Immunology 106, n. 2 (giugno 2002): 159–72. http://dx.doi.org/10.1046/j.1365-2567.2002.01422.x.

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32

Gagliardi, Maria Cristina, Raffaela Teloni, Federico Giannoni, Sabrina Mariotti, Maria Elena Remoli, Valeria Sargentini, Melissa Videtta et al. "Mycobacteria Exploit p38 Signaling To Affect CD1 Expression and Lipid Antigen Presentation by Human Dendritic Cells". Infection and Immunity 77, n. 11 (31 agosto 2009): 4947–52. http://dx.doi.org/10.1128/iai.00607-09.

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Abstract (sommario):

ABSTRACT Group I CD1 proteins are specialized antigen-presenting molecules that present both microbial and self lipid antigens to CD1-restricted α/β T lymphocytes. The production of high levels of gamma interferon and lysis of infected macrophages by lipid-specific T lymphocytes are believed to play pivotal roles mainly in the defense against mycobacterial infections. We previously demonstrated that Mycobacterium tuberculosis and bacillus Calmette-Guérin (Mycobacterium bovis BCG) induce human monocytes to differentiate into CD1− dendritic cells (DC), which cannot present lipid antigens to specific T cells. Here, we show that in human monocytes mycobacteria trigger phosphorylation of p38 mitogen-activated protein kinase to inhibit CD1 expression in DC derived from infected monocytes. Pretreatment with a specific p38 inhibitor renders monocytes insensitive to mycobacterial subversion and allows them to differentiate into CD1+ DC, which are fully capable of presenting lipid antigens to specific T cells. We also report that one of the pathogen recognition receptors triggered by BCG to activate p38 is complement receptor 3 (CR3), as shown by reduced p38 phosphorylation and partial reestablishment of CD1 membrane expression obtained by CR3 blockade before infection. In conclusion, we propose that p38 signaling is a novel pathway exploited by mycobacteria to affect the expression of CD1 antigen-presenting cells and avoid immune recognition.

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33

Sieling, Peter A., Robert Hunger e Robert L. Modlin. "Human CD1-restricted T cells from leprosy lesions display distinct and complementary functions in comparison to MHC-restricted T cells (129.28)". Journal of Immunology 182, n. 1_Supplement (1 aprile 2009): 129.28. http://dx.doi.org/10.4049/jimmunol.182.supp.129.28.

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Abstract (sommario):

Abstract CD1 proteins are a family of MHC-like polypeptides that present lipids rather than peptides to T cells. We have examined the role of CD1-restricted T cells in the context of mycobacterial infection since T cells mediate host defense against mycobacterial infection and the mycobacterial envelope contains a high concentration of lipids. To determine whether CD1 and MHC-restricted T cells represent distinct or complementary functional populations, T cells derived from lesions of leprosy patients were activated through their CD3 receptor, gene expression patterns were evaluated, and protein expression measured using ELISA. CD1- and MHC-restricted T cells exhibited a similar profile of cytokine production, particularly Th1 and Th2 cytokines. In contrast, the two populations of T cells were more distinct in their chemokine expression. CD1-restricted T cells produced CCL20, which shares a receptor with antimicrobial β-defensins; in contrast, MHC-restricted T cells produced CXCL10, a chemokine whose receptor is expressed on activated Th1 T cells. Our data reveal both complementary and distinct functions of CD1- and MHC-restricted T cells and suggest that CD1-restricted T cells function in the rapid response to microbial infection in contrast to MHC-restricted T cells, which regulate adaptive immunity.

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34

Young, David C., e D. Branch Moody. "T-cell recognition of glycolipids presented by CD1 proteins". Glycobiology 16, n. 7 (5 aprile 2006): 103R—112R. http://dx.doi.org/10.1093/glycob/cwj111.

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35

Garzón, Diana, Claudio Anselmi, Peter J. Bond e José D. Faraldo-Gómez. "Dynamics of the Antigen-binding Grooves in CD1 Proteins". Journal of Biological Chemistry 288, n. 27 (15 maggio 2013): 19528–36. http://dx.doi.org/10.1074/jbc.m113.470179.

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36

LUNDGREN-AKERLUND, E., A. M. OLOFSSON, E. BERGER e K. E. ARFORS. "CD1 1b/CD18-Dependent Polymorphonuclear Leucocyte Interaction with Matrix Proteins in Adhesion and Migration". Scandinavian Journal of Immunology 37, n. 5 (maggio 1993): 569–74. http://dx.doi.org/10.1111/j.1365-3083.1993.tb02573.x.

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Maître, Blandine, Catherine Angénieux, Virginie Wurtz, Emilie Layre, Martine Gilleron, Anthony Collmann, Sabrina Mariotti et al. "The assembly of CD1e is controlled by an N-terminal propeptide which is processed in endosomal compartments". Biochemical Journal 419, n. 3 (14 aprile 2009): 661–68. http://dx.doi.org/10.1042/bj20082204.

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Abstract (sommario):

CD1e displays unique features in comparison with other CD1 proteins. CD1e accumulates in Golgi compartments of immature dendritic cells and is transported directly to lysosomes, where it is cleaved into a soluble form. In these latter compartments, CD1e participates in the processing of glycolipid antigens. In the present study, we show that the N-terminal end of the membrane-associated molecule begins at amino acid 20, whereas the soluble molecule consists of amino acids 32–333. Thus immature CD1e includes an N-terminal propeptide which is cleaved in acidic compartments and so is absent from its mature endosomal form. Mutagenesis experiments demonstrated that the propeptide controls the assembly of the CD1e α-chain with β2-microglobulin, whereas propeptide-deleted CD1e molecules are immunologically active. Comparison of CD1e cDNAs from different mammalian species indicates that the CD1e propeptide is conserved during evolution, suggesting that it may also optimize the generation of CD1e molecules in other species.

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Strominger, Jack L. "An Alternative Path for Antigen Presentation: Group 1 CD1 Proteins". Journal of Immunology 184, n. 7 (19 marzo 2010): 3303–5. http://dx.doi.org/10.4049/jimmunol.1090008.

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39

van Dongen, J. J., T. Quertermous, C. R. Bartram, D. P. Gold, I. L. Wolvers-Tettero, W. M. Comans-Bitter, H. Hooijkaas, H. J. Adriaansen, A. de Klein e A. Raghavachar. "T cell receptor-CD3 complex during early T cell differentiation. Analysis of immature T cell acute lymphoblastic leukemias (T-ALL) at DNA, RNA, and cell membrane level." Journal of Immunology 138, n. 4 (15 febbraio 1987): 1260–69. http://dx.doi.org/10.4049/jimmunol.138.4.1260.

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Abstract (sommario):

Abstract T cell acute lymphoblastic leukemias (T-ALL) can be regarded as the malignant counterparts of cells in various T cell differentiation stages. To study the expression of the human T cell receptor (TcR)-CD3 complex during the early stages of T cell differentiation, we have analyzed 22 T-ALL at the cell membrane level and the DNA level and 12 of them at the RNA level. According to their immunologic phenotype, the T-ALL could be divided into three main groups: 10 immature T-ALL (CD1-/CD3-), seven common thymocytic T-ALL (CD1+/CD3-or+), and five mature T-ALL (CD1-/CD3+). Among the 10 immature T-ALL three appeared to express the immunologic phenotype of the putative prothymocyte (TdT+/HLA-DR+/CD7+/CD2+/CD5-/CD1-/CD3-), whereas the other seven T-ALL appeared to be immature thymocytic (TdT+/HLA-DR-/CD7+/CD2+/CD5+/CD1-/CD3-). Transcripts of the CD3-delta and CD3-epsilon genes were present in all CD3- and CD3+ T-ALL tested, including prothymocytic T-ALL. However, prothymocytic T-ALL had germline TcR-beta genes and were not rearranged to the characterized TcR-gamma joining regions. The presence of CD3 transcripts and absence of TcR gene rearrangements in prothymocytic T-ALL supports their immature T cell character. Two immature thymocytic T-ALL also had germline TcR-gamma genes and one of them had germline TcR-beta genes. In all other T-ALL the TcR-gamma and TcR-beta genes were rearranged. The presumptive functional 1.3-kilobase TcR-beta transcripts were detected in the majority of T-ALL with rearranged TcR-beta genes. Distinct levels of TcR-gamma transcripts appeared to be present only in some thymocytic T-ALL, i.e., some immature thymocytic T-ALL and common thymocytic T-ALL. TcR-alpha mRNA could only be detected in CD3+ mature T-ALL, but was absent in all CD3+ common thymocytic T-ALL tested. Our data indicate that CD3 gene transcription is one of the earliest events during T cell differentiation and already occurs in prothymocytes. The TcR-gamma and TcR-beta genes rearrange early during thymocytic differentiation and can subsequently be transcribed. High levels of TcR-gamma gene transcription may only occur in a part of the T cells during thymic differentiation, while TcR-beta gene transcription continues during further differentiation. TcR-alpha gene transcription may be the final step in the production of the complete set of TcR and CD3 proteins, resulting in the expression of the TcR alpha beta-CD3 complex at the cell surface of mature T cells.(ABSTRACT TRUNCATED AT 400 WORDS)

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Cacciatore, Ivana, Sonia Spalletta, Annalisa Di Rienzo, Vincenzo Flati, Erika Fornasari, Laura Pierdomenico, Piero Del Boccio et al. "Anti-Obesity and Anti-Inflammatory Effects of Novel Carvacrol Derivatives on 3T3-L1 and WJ-MSCs Cells". Pharmaceuticals 16, n. 3 (22 febbraio 2023): 340. http://dx.doi.org/10.3390/ph16030340.

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Abstract (sommario):

(1) Background: Obesity, a complex metabolic disease resulting from an imbalance between food consumption and energy expenditure, leads to an increase in adipocytes and chronic inflammatory conditions. The aim of this paper was to synthesize a small series of carvacrol derivatives (CD1-3) that are able to reduce both adipogenesis and the inflammatory status often associated with the progression of the obesity disease. (2) Methods: The synthesis of CD1-3 was performed using classical procedures in a solution phase. Biological studies were performed on three cell lines: 3T3-L1, WJ-MSCs, and THP-1. The anti-adipogenic properties of CD1-3 were evaluated using western blotting and densitometric analysis by assessing the expression of obesity-related proteins, such as ChREBP. The anti-inflammatory effect was estimated by measuring the reduction in TNF-α expression in CD1-3-treated THP-1 cells. (3) Results: CD1-3—obtained through a direct linkage between the carboxylic moiety of anti-inflammatory drugs (Ibuprofen, Flurbiprofen, and Naproxen) and the hydroxyl group of carvacrol—have an inhibitory effect on the accumulation of lipids in both 3T3-L1 and WJ-MSCs cell cultures and an anti-inflammatory effect by reducing TNF- α levels in THP-1 cells. (4) Conclusions: Considering the physicochemical properties, stability, and biological data, the CD3 derivative—obtained by a direct linkage between carvacrol and naproxen—resulted in the best candidate, displaying anti-obesity and anti-inflammatory effects in vitro.

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Sée, Violaine, Nina K. M. Rajala, David G. Spiller e Michael R. H. White. "Calcium-dependent regulation of the cell cycle via a novel MAPK–NF-κB pathway in Swiss 3T3 cells". Journal of Cell Biology 166, n. 5 (23 agosto 2004): 661–72. http://dx.doi.org/10.1083/jcb.200402136.

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Abstract (sommario):

Nuclear factor kappa B (NF-κB) has been implicated in the regulation of cell proliferation and transformation. We investigated the role of the serum-induced intracellular calcium increase in the NF-κB–dependent cell cycle progression in Swiss 3T3 fibroblasts. Noninvasive photoactivation of a calcium chelator (Diazo-2) was used to specifically disrupt the transient rise in calcium induced by serum stimulation of starved Swiss 3T3 cells. The serum-induced intracellular calcium peak was essential for subsequent NF-κB activation (measured by real-time imaging of the dynamic p65 and IκBα fluorescent fusion proteins), cyclin D1 (CD1) promoter-directed transcription (measured by real-time luminescence imaging of CD1 promoter-directed firefly luciferase activity), and progression to cell division. We further showed that the serum-induced mitogen-activated protein kinase (MAPK) phosphorylation is calcium dependent. Inhibition of the MAPK- but not the PtdIns3K-dependent pathway inhibited NF-κB signaling, and further, CD1 transcription and cell cycle progression. These data suggest that a serum-dependent calcium signal regulates the cell cycle via a MAPK–NF-κB pathway in Swiss 3T3 cells.

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42

Tysoe-Calnon, V. A., J. E. Grundy e S. J. Perkins. "Molecular comparisons of the β2-microglobulin-binding site in class I major-histocompatibility-complex α-chains and proteins of related sequences". Biochemical Journal 277, n. 2 (15 luglio 1991): 359–69. http://dx.doi.org/10.1042/bj2770359.

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Abstract (sommario):

beta 2-Microglobulin (beta 2m) binds non-covalently to the alpha 1, alpha 2 and alpha 3 domains of the alpha-chain of Class I major-histocompatibility-complex (MHC) molecules. On the basis of the crystal structures of human leucocyte antigens HLA-A2.1 and HLA-Aw68.1, we have used molecular-graphics analyses to define 44 contact points between 19 alpha-chain residues and 18 beta 2m residues. In 88 other alpha-chain sequences from the HLA-A, HLA-B, HLA-C, HLA-D, HLA-E, HLA-F and HLA-G locus products in man and the H-2, Qa and Tla loci in mouse, 37 contact sites were conserved to 90% or more, and in beta 2m sequences from seven other species 40% of contact sites were totally conserved. Four distinct regions form the contact points between the alpha-chain and beta 2m, one on each of the alpha 1 and alpha 2 domains and two on the alpha 3 domain. We have further studied the alpha-chain sequences of three non-MHC molecules, human CD1 and rat Fc receptor (FcRn), known to bind to beta 2m, and a third molecule, the putative product of the H301 (UL18) gene of human cytomegalovirus (CMV). CMV has been shown to bind beta 2m, and it has been postulated that the H301-gene product, which has sequence similarity to Class I HLA, is the protein responsible. These sequences exhibited much lower residue conservation with the MHC-linked group, although the alpha 3 domain was the most highly conserved, and gaps and insertions were required for optimal alignments with the 90 alpha-chain sequences. Of the 44 beta 2m-alpha-chain contacts defined for Class I HLA, 24 alpha-chain contact sites were conserved in CD1, 25 in FcRn and 17 in the H301-gene product. For CD1 and FcRn, the majority of the conserved beta 2m contacts were found in the alpha 2 domain and the major contact region in the alpha 3 domain. Together with the use of secondary-structure predictions, it was concluded that the binding of beta 2m in CD1 and FcRn was MHC-like at the alpha 3 domain, and probably also at the alpha 2 domain for FcRn, but non-MHC-like for the alpha 1 domain of both molecules and the alpha 2 domain of CD1. In the H301-gene product sequence, only the beta 2m contacts with the main region of the alpha 3 domain were noticeably conserved.(ABSTRACT TRUNCATED AT 400 WORDS)

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43

Teyton, Luc. "Role of lipid transfer proteins in loading CD1 antigen-presenting molecules". Journal of Lipid Research 59, n. 8 (19 marzo 2018): 1367–73. http://dx.doi.org/10.1194/jlr.r083212.

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44

Timkovich, Russell. "Proton NMR investigation of cytochrome cd1 complexes with electron-donor proteins". Biochemistry 25, n. 5 (11 marzo 1986): 1089–93. http://dx.doi.org/10.1021/bi00353a022.

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45

Chintalapati, Krishnam Raju, Yesudas Kada, Vasavi Malkhed, Sanath Kumar Goud Palusa, Rabin Bera e V. Shanmukha Kumar Jagarlapudi. "In silico Studies of Cilnidipine Degradation Products for Structure Confirmation, Toxicity Prediction and Molecular Docking". Asian Journal of Chemistry 36, n. 4 (30 marzo 2024): 865–78. http://dx.doi.org/10.14233/ajchem.2024.31150.

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Abstract (sommario):

In this study, a comprehensive analysis of cilnidipine and its degradation products (KD1-KD4 and CD1-CD3) with three main objectives viz. (i) toxicity prediction for bacterial mutagenicity, (ii) assessment of pharmacological activity and (iii) density functional theory (DFT) calculations were performed for structure confirmation. For bacterial mutagenicity prediction, in silico assessments were performed following ICH M7 guidelines. Using rule-based and statistical-based methodologies, predictions revealed an alerting group in CD1-CD3, while no alerting group was observed in KD1-KD4 for bacterial mutagenicity. To assess pharmacological activity, docking studies were conducted to identify the mode of binding and interaction types of cilnidipine and its degradation products with N-type and L-type calcium channel subunits 7VFS and 7UHF, respectively. Additionally, 20 drugs acting as calcium channel blockers were considered for docking analysis to correlate the affinities of binding. The interaction energies revealed that molecule CD3 shows the highest binding affinity with the ligand molecules, with a binding energy of -9.2 (kcal/mol) with 7VFS and -8.7 (kcal/mol) with 7UHF proteins, followed by KD3 with a binding energy of -8.7 (kcal/mol) (7VFS) and -7.9 (kcal/mol) (7UHF). Furthermore, DFT calculations were employed to reassess the structures of degradation products CD1 and CD2 proposed in the literature. Simulating 1H and 13C NMR spectra, the obtained data demonstrated good agreement with experimental results, confirming the proposed stereo-configurations in the literature. Based on in silico bacterial mutagenicity predictions and docking studies, KD3 emerged as a promising compound for receptor binding. Additionally, DFT calculations provided structural insights, affirming stereo-configurations proposed in the existing literature. This multifaceted approach contributed valuable insights into the toxicity, pharmacology and structural aspects of cilnidipine degradation products.

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46

Bonati, A., P. Zanelli, S. Ferrari, A. Plebani, B. Starcich, M. Savi e TM Neri. "T-cell receptor beta-chain gene rearrangement and expression during human thymic ontogenesis". Blood 79, n. 6 (15 marzo 1992): 1472–83. http://dx.doi.org/10.1182/blood.v79.6.1472.1472.

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Abstract (sommario):

Abstract T-cell receptor (TCR) beta-chain proteins appear early (approximately 15th week of gestation) during human thymic ontogenesis. These beta- chain proteins, which appear before terminal deoxynucleotidyl transferase (TdT), could be an expression of a fully rearranged (V-D- J), incompletely rearranged (D-J), or germline TCR beta-chain gene. The aims of this study, performed from the 15th week onward, were the following: (1) to investigate whether or not TCR beta gene rearranges at an early stage during human thymic ontogenesis; (2) to investigate whether complete presumptive functional (1.3 kb) TCR beta gene transcript is present at these early stages of development, or if incomplete (1 kb) or germ-line (1.1 kb) transcripts are expressed; (3) to examine the phenotype of TCR beta-chain+ cells with two-color fluorescence using monoclonal antibody (MoAb) beta F1 and MoAbs that recognize CD1, CD2, CD3, CD4, CD8, CD5, and CD7 antigens (rabbit anti- calf TdT antiserum was used to detect TdT); and (4) to demonstrate whether or not beta gene N-diversity regions are detectable as early as the 15th week and whether or not N-nucleotide insertions correlate to TdT expression. Fifteen- to 22-week fetal thymuses and pediatric thymuses were investigated. We demonstrated that TCR beta-chain gene rearranged as early as the 15th week in human thymus and that a complete functional TCR beta gene transcript was expressed at these early stages of human development. No other analyses to date have investigated TCR beta gene expression in early human thymus using molecular biology techniques. No significant differences were detectable between phenotypic analysis of fetal and pediatric samples, except for TdT expression, which appeared after the 20th week. Essentially all mCD3+ (OKT3+) cells were beta-chain+ at the different weeks investigated. A significant percentage of CD1+ cells were beta- chain+, and the percentage increased along with the age of development. After the 20th week, we identified three main populations: TdT+, cCD3+, beta F-(early thymic precursors); TdT+, CD1+, beta F1+ (intermediate maturity cortical thymocytes); and TdT-, mCD3+, beta F1++ (mature medullary thymocytes). Given these values, we may consider beta-chain expression an ordered process. beta gene N-nucleotide insertions were correlated to TdT expression, since N-regions increased considerably after the 20th week. A further increase of N-nucleotide insertions was detected from the 22nd week to the 32nd week.

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47

Bonati, A., P. Zanelli, S. Ferrari, A. Plebani, B. Starcich, M. Savi e TM Neri. "T-cell receptor beta-chain gene rearrangement and expression during human thymic ontogenesis". Blood 79, n. 6 (15 marzo 1992): 1472–83. http://dx.doi.org/10.1182/blood.v79.6.1472.bloodjournal7961472.

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Abstract (sommario):

T-cell receptor (TCR) beta-chain proteins appear early (approximately 15th week of gestation) during human thymic ontogenesis. These beta- chain proteins, which appear before terminal deoxynucleotidyl transferase (TdT), could be an expression of a fully rearranged (V-D- J), incompletely rearranged (D-J), or germline TCR beta-chain gene. The aims of this study, performed from the 15th week onward, were the following: (1) to investigate whether or not TCR beta gene rearranges at an early stage during human thymic ontogenesis; (2) to investigate whether complete presumptive functional (1.3 kb) TCR beta gene transcript is present at these early stages of development, or if incomplete (1 kb) or germ-line (1.1 kb) transcripts are expressed; (3) to examine the phenotype of TCR beta-chain+ cells with two-color fluorescence using monoclonal antibody (MoAb) beta F1 and MoAbs that recognize CD1, CD2, CD3, CD4, CD8, CD5, and CD7 antigens (rabbit anti- calf TdT antiserum was used to detect TdT); and (4) to demonstrate whether or not beta gene N-diversity regions are detectable as early as the 15th week and whether or not N-nucleotide insertions correlate to TdT expression. Fifteen- to 22-week fetal thymuses and pediatric thymuses were investigated. We demonstrated that TCR beta-chain gene rearranged as early as the 15th week in human thymus and that a complete functional TCR beta gene transcript was expressed at these early stages of human development. No other analyses to date have investigated TCR beta gene expression in early human thymus using molecular biology techniques. No significant differences were detectable between phenotypic analysis of fetal and pediatric samples, except for TdT expression, which appeared after the 20th week. Essentially all mCD3+ (OKT3+) cells were beta-chain+ at the different weeks investigated. A significant percentage of CD1+ cells were beta- chain+, and the percentage increased along with the age of development. After the 20th week, we identified three main populations: TdT+, cCD3+, beta F-(early thymic precursors); TdT+, CD1+, beta F1+ (intermediate maturity cortical thymocytes); and TdT-, mCD3+, beta F1++ (mature medullary thymocytes). Given these values, we may consider beta-chain expression an ordered process. beta gene N-nucleotide insertions were correlated to TdT expression, since N-regions increased considerably after the 20th week. A further increase of N-nucleotide insertions was detected from the 22nd week to the 32nd week.

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48

Reinink, Peter, Adam Shahine, Stephanie Gras, Tan-Yun Cheng, Rachel Farquhar, Kattya Lopez, Sara A. Suliman et al. "A TCR β-Chain Motif Biases toward Recognition of Human CD1 Proteins". Journal of Immunology 203, n. 12 (6 novembre 2019): 3395–406. http://dx.doi.org/10.4049/jimmunol.1900872.

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49

Briken, Volker, D. Branch Moody e Steven A. Porcelli. "Diversification of CD1 proteins: sampling the lipid content of different cellular compartments". Seminars in Immunology 12, n. 6 (dicembre 2000): 517–25. http://dx.doi.org/10.1006/smim.2000.0274.

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50

Sloand, Elaine M., Loretta Pfannes, Gubin Chen, Simant Shah, Elena E. Solomou, John Barrett e Neal S. Young. "CD34 cells from patients with trisomy 8 myelodysplastic syndrome (MDS) express early apoptotic markers but avoid programmed cell death by up-regulation of antiapoptotic proteins". Blood 109, n. 6 (7 novembre 2006): 2399–405. http://dx.doi.org/10.1182/blood-2006-01-030643.

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Abstract (sommario):

Abstract CD34 cells from patients with trisomy 8 myelodysplastic syndrome (MDS) are distinguished from other MDS cells and from normal hematopoietic cells by their pronounced expression of apoptotic markers. Paradoxically, trisomy 8 clones can persist in patients with bone marrow failure and expand following immunosuppression. We previously demonstrated up-regulation of c-myc and CD1 by microarray analysis. Here, we confirmed these findings by real-time polymerase chain reaction (PCR), demonstrated up-regulation of survivin, c-myc, and CD1 protein expression, and documented comparable colony formation by annexin+ trisomy 8− CD34+ and annexin− CD34 cells. There were low levels of DNA degradation in annexin+ trisomy 8 CD34 cells, which were comparable with annexin− CD34 cells. Trisomy 8 cells were resistant to apoptosis induced by gamma irradiation. Knock-down of survivin by siRNA resulted in preferential loss of trisomy 8 cells. These results suggest that trisomy 8 cells undergo incomplete apoptosis and are nonetheless capable of colony formation and growth.

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