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Journal articles on the topic 'Antibody functional repertoire'

Author: Grafiati

Published: 14 March 2023

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1

Raybould, Matthew I. J., Claire Marks, Aleksandr Kovaltsuk, Alan P. Lewis, Jiye Shi, and Charlotte M. Deane. "Public Baseline and shared response structures support the theory of antibody repertoire functional commonality." PLOS Computational Biology 17, no. 3 (2021): e1008781. http://dx.doi.org/10.1371/journal.pcbi.1008781.

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The naïve antibody/B-cell receptor (BCR) repertoires of different individuals ought to exhibit significant functional commonality, given that most pathogens trigger an effective antibody response to immunodominant epitopes. Sequence-based repertoire analysis has so far offered little evidence for this phenomenon. For example, a recent study estimated the number of shared (‘public’) antibody clonotypes in circulating baseline repertoires to be around 0.02% across ten unrelated individuals. However, to engage the same epitope, antibodies only require a similar binding site structure and the pres

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Collins, Andrew M., Yan Wang, Krishna M. Roskin, Christopher P. Marquis, and Katherine J. L. Jackson. "The mouse antibody heavy chain repertoire is germline-focused and highly variable between inbred strains." Philosophical Transactions of the Royal Society B: Biological Sciences 370, no. 1676 (2015): 20140236. http://dx.doi.org/10.1098/rstb.2014.0236.

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The human and mouse antibody repertoires are formed by identical processes, but like all small animals, mice only have sufficient lymphocytes to express a small part of the potential antibody repertoire. In this study, we determined how the heavy chain repertoires of two mouse strains are generated. Analysis of IgM- and IgG-associated VDJ rearrangements generated by high-throughput sequencing confirmed the presence of 99 functional immunoglobulin heavy chain variable (IGHV) genes in the C57BL/6 genome, and inferred the presence of 164 IGHV genes in the BALB/c genome. Remarkably, only five IGHV

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3

Robinson, William H. "Sequencing the functional antibody repertoire—diagnostic and therapeutic discovery." Nature Reviews Rheumatology 11, no. 3 (2014): 171–82. http://dx.doi.org/10.1038/nrrheum.2014.220.

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4

Zheng, Tianqing, Jia Xie, Zhuo Yang, et al. "Antibody selection using clonal cocultivation of Escherichia coli and eukaryotic cells in miniecosystems." Proceedings of the National Academy of Sciences 115, no. 27 (2018): E6145—E6151. http://dx.doi.org/10.1073/pnas.1806718115.

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We describe a method for the rapid selection of functional antibodies. The method depends on the cocultivation of Escherichia coli that produce phage with target eukaryotic cells in very small volumes. The antibodies on phage induce selectable phenotypes in the target cells, and the nature of the antibody is determined by gene sequencing of the phage genome. To select functional antibodies from the diverse antibody repertoire, we devised a selection platform that contains millions of picoliter-sized droplet ecosystems. In each miniecosystem, the bacteria produce phage displaying unique members

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de Bourcy, Charles F. A., Cesar J. Lopez Angel, Christopher Vollmers, Cornelia L. Dekker, Mark M. Davis, and Stephen R. Quake. "Phylogenetic analysis of the human antibody repertoire reveals quantitative signatures of immune senescence and aging." Proceedings of the National Academy of Sciences 114, no. 5 (2017): 1105–10. http://dx.doi.org/10.1073/pnas.1617959114.

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The elderly have reduced humoral immunity, as manifested by increased susceptibility to infections and impaired vaccine responses. To investigate the effects of aging on B-cell receptor (BCR) repertoire evolution during an immunological challenge, we used a phylogenetic distance metric to analyze Ig heavy-chain transcript sequences in both young and elderly individuals before and after influenza vaccination. We determined that BCR repertoires become increasingly specialized over a span of decades, but less plastic. In 50% of the elderly individuals, a large space in the repertoire was occupied

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Schwimmer, Lauren J., Betty Huang, Hoa Giang, et al. "Discovery of diverse and functional antibodies from large human repertoire antibody libraries." Journal of Immunological Methods 391, no. 1-2 (2013): 60–71. http://dx.doi.org/10.1016/j.jim.2013.02.010.

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7

Nobrega, Alberto, Alf Grandien, Matthias Haury, Laura Hecker, Evelyne Malanchère, and Antonio Coutinho. "Functional diversity and clonal frequencies of reactivity in the available antibody repertoire." European Journal of Immunology 28, no. 4 (1998): 1204–15. http://dx.doi.org/10.1002/(sici)1521-4141(199804)28:04<1204::aid-immu1204>3.0.co;2-g.

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Kodangattil, Sreekumar, Christine Huard, Cindy Ross, et al. "The functional repertoire of rabbit antibodies and antibody discovery via next-generation sequencing." mAbs 6, no. 3 (2014): 628–36. http://dx.doi.org/10.4161/mabs.28059.

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9

Maleckar, J. R., and L. A. Sherman. "The composition of the T cell receptor repertoire in nude mice." Journal of Immunology 138, no. 11 (1987): 3873–76. http://dx.doi.org/10.4049/jimmunol.138.11.3873.

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Abstract Previous results from several laboratories have demonstrated the presence of functional T lymphocytes in congenitally athymic (nude) mice. The present study represents an analysis of the T cell receptor repertoire exhibited by such cells. Clones of H-2Kb-specific cytotoxic T lymphocytes (CTL) were generated under primary limiting dilution conditions by using spleen cells from nude mice. These clones were analyzed on a panel of Kb mutant target cells to assess the receptor specificity of each clone. Unlike thymic bearing mice the CTL repertoires of which are exceedingly diverse, it was

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Kirchenbaum, Greg A., Giuseppe A. Sautto, Rodrigo B. Abreu, Paul V. Lehmann, and Ted M. Ross. "Assessment of Antibody Functional Affinity using FluoroSpot." Journal of Immunology 204, no. 1_Supplement (2020): 86.11. http://dx.doi.org/10.4049/jimmunol.204.supp.86.11.

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Abstract Studies of B cell immunity often rely upon serologic methodologies that primarily assess antibody specificity. However, functional affinity of the antigen-specific antibody repertoire is a key determinant of protective efficacy. Presently, detailed assessment of single B cell/antibody functional affinity is labor-intensive and low-throughput. Therefore, we sought to evaluate whether B cell FluoroSpot assays would enable distinction between B cells with differential functional affinity since fluorescent intensity is directly proportional to antibody abundance in this assay. To test our

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11

Reinhardt, Richard Lee, Hong-Erh Liang, and Richard M. Locksley. "Cytokine-secreting follicular T cells shape the antibody repertoire (34.19)." Journal of Immunology 182, no. 1_Supplement (2009): 34.19. http://dx.doi.org/10.4049/jimmunol.182.supp.34.19.

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Abstract High-affinity antibodies are critical for host protection against pathogens and toxins, and underlie successful vaccines. Generation of such antibodies requires T cell-dependent help, which mediates germinal center (GC) reactions where mutation and selection of B cells expressing receptors with high-affinity for antigen occurs. Follicular CD4 T (TFH) cells, which comprise only 5-10% of GC cells, have been imaged in stable conjugates with GC B cells, but no functional analysis of B/TFH cell interactions in GC has been performed. Using an IL-4 reporter system, we show that TFH cells com

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12

Bai, Xuelian, Moonseon Jang, Nam Ju Lee, et al. "A Novel Synthetic Antibody Library with Complementarity-Determining Region Diversities Designed for an Improved Amplification Profile." International Journal of Molecular Sciences 23, no. 11 (2022): 6255. http://dx.doi.org/10.3390/ijms23116255.

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Antibody discovery by phage display consists of two phases, i.e., the binding phase and the amplification phase. Ideally, the selection process is dominated by the former, and all the retrieved clones are amplified equally during the latter. In reality, the amplification efficiency of antibody fragments varies widely among different sequences and, after a few rounds of phage display panning, the output repertoire often includes rapidly amplified sequences with low or no binding activity, significantly diminishing the efficiency of antibody isolation. In this work, a novel synthetic single-chai

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13

Gould, Hannah J., and Yu-Chang Bryan Wu. "IgE repertoire and immunological memory: compartmental regulation and antibody function." International Immunology 30, no. 9 (2018): 403–12. http://dx.doi.org/10.1093/intimm/dxy048.

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Abstract It is now generally recognized that bone marrow is the survival niche for antigen-specific plasma cells with long-term immunological memory. These cells release antibodies into the circulation, needed to prime effector cells in the secondary immune response. These antibodies participate in the surveillance for antigen and afford immune defence against pathogens and toxins previously encountered in the primary immune response. IgE antibodies function together with their effector cells, mast cells, to exert ‘immediate hypersensitivity’ in mucosal tissues at the front line of immune defe

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Gilchuk, Pavlo, Charles D. Murin, Jacob C. Milligan, et al. "Structural and functional analysis of cooperativity in a potent human antibody cocktail against Ebola virus." Journal of Immunology 204, no. 1_Supplement (2020): 167.19. http://dx.doi.org/10.4049/jimmunol.204.supp.167.19.

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Abstract Structural principles underlying the composition of protective antiviral monoclonal antibody (mAb) cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic mAb cocktail against Ebola virus (EBOV). Systematic analysis of antibody repertoire in the human survivors identified a pair of potently neutralizing mAbs that cooperatively bind to the ebolavirus glycoprotein (GP). High-resolution structures revealed that in a two-antibody cocktail, molecular mimicry was a major feature of mAb/GP interactions. Broadly neutralizing mAb rEBOV-520 targeted a co

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15

Kalled, S. L., and P. H. Brodeur. "Utilization of V kappa families and V kappa exons. Implications for the available B cell repertoire." Journal of Immunology 147, no. 9 (1991): 3194–200. http://dx.doi.org/10.4049/jimmunol.147.9.3194.

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Abstract A molecular cloning approach was used to determine the relative utilization of 2 individual V kappa 21 genes, 13 V kappa gene families, and the 4 functional J kappa gene segments among splenic B cells of nonimmunized BALB/c mice. Based on the observed frequency of individual V kappa gene expression, we estimate that the mouse genome encodes 150 to 180 functional V kappa genes, and we suggest that most functional V kappa exons are expressed at comparable frequencies in the preimmune antibody repertoire. In contrast, clear differences in J kappa segment utilization were observed, J kapp

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16

Zwirner, J., W. Weissenhorn, L. Karlsson, et al. "Expression of a functional chimeric Ig-MHC class II protein." Journal of Immunology 148, no. 1 (1992): 272–76. http://dx.doi.org/10.4049/jimmunol.148.1.272.

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Abstract We have generated a chimeric protein molecule composed of the alpha- and beta-chains of the MHC class II I-E molecule fused to antibody V regions derived from anti-human CD4 mAb MT310. Expression vectors were constructed containing the functional, rearranged gene segments coding for the V region domains of the antibody H and L chains in place of the first domains of the complete structural genes of the I-E alpha- and beta-chains, respectively. Cells transfected with both hybrid genes expressed a stable protein product on the cell surface. The chimeric molecule exhibited the idiotype o

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Hooijkaas, H., A. A. van der Linde-Preesman, W. M. Bitter, R. Benner, J. R. Pleasants, and B. S. Wostmann. "Frequency analysis of functional immunoglobulin C- and V-gene expression by mitogen-reactive B cells in germfree mice fed chemically defined ultra-filtered "antigen-free" diet." Journal of Immunology 134, no. 4 (1985): 2223–27. http://dx.doi.org/10.4049/jimmunol.134.4.2223.

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Abstract The frequencies of lipopolysaccharide (LPS)-reactive B cells and their antibody specificity repertoire have been determined in the spleen and bone marrow (BM) of conventional (CV) and "antigen-free" C3H/HeCr mice of various ages. The antigen-free mice were germfree (GF)-raised and were fed an ultrafiltered solution of chemically defined (CD) low m.w. nutrients, and were thus devoid of exogenous antigenic stimulation. Spleen and BM cells were grown in a limiting dilution culture system that allows the growth and development of every newly formed LPS-reactive B cell into a clone of IgM-

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18

Lacroix-Desmazes, Sébastien, Igor Resnick, Dorothea Stahl, et al. "Defective Self-Reactive Antibody Repertoire of Serum IgM in Patients with Hyper-IgM Syndrome." Journal of Immunology 162, no. 9 (1999): 5601–8. http://dx.doi.org/10.4049/jimmunol.162.9.5601.

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Abstract We have analyzed the self-reactive repertoires of IgM and IgG Abs in the serum of 19 patients with hyper-IgM syndrome (HIM) by means of a quantitative immunoblotting technique that allows for a quantitative comparison of Ab repertoires in health and disease by multiparametric statistical analysis. Normal tissue extracts of liver, lung, stomach, and kidney were used as sources of self Ags. Extracts of Pseudomonas aeruginosa and Staphylococcus epidermidis were used as sources of nonself Ags. We demonstrate a significant bias in repertoires of reactivities of IgM of patients with HIM wit

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19

Nielsen, Morten A., Lasse S. Vestergaard, John Lusingu, et al. "Geographical and Temporal Conservation of Antibody Recognition of Plasmodium falciparum Variant Surface Antigens." Infection and Immunity 72, no. 6 (2004): 3531–35. http://dx.doi.org/10.1128/iai.72.6.3531-3535.2004.

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ABSTRACT The slow acquisition of protection against Plasmodium falciparum malaria probably reflects the extensive diversity of important antigens. The variant surface antigens (VSA) that mediate parasite adhesion to a range of host molecules are regarded as important targets of acquired protective immunity, but their diversity makes them questionable vaccine candidates. We determined levels of VSA-specific immunoglobulin G (IgG) in human plasma collected at four geographically distant and epidemiologically distinct localities with specificity for VSA expressed by P. falciparum isolates from th

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20

Papp, Krisztián, Péter Végh, Kata Miklós, et al. "Detection of Complement Activation on Antigen Microarrays Generates Functional Antibody Profiles and Helps Characterization of Disease-Associated Changes of the Antibody Repertoire." Journal of Immunology 181, no. 11 (2008): 8162–69. http://dx.doi.org/10.4049/jimmunol.181.11.8162.

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21

Kumar, Rashmi, Martina P. Bach, Federica Mainoldi, et al. "Antibody repertoire diversification through VH gene replacement in mice cloned from an IgA plasma cell." Proceedings of the National Academy of Sciences 112, no. 5 (2015): E450—E457. http://dx.doi.org/10.1073/pnas.1417988112.

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In mammals, VDJ recombination is responsible for the establishment of a highly diversified preimmune antibody repertoire. Acquisition of a functional Ig heavy (H) chain variable (V) gene rearrangement is thought to prevent further recombination at the IgH locus. Here, we describe VHQ52NT; Vκgr32NT Ig monoclonal mice reprogrammed from the nucleus of an intestinal IgA+ plasma cell. In VHQ52NT mice, IgA replaced IgM to drive early B-cell development and peripheral B-cell maturation. In VHQ52NT animals, over 20% of mature B cells disrupted the single productive, nonautoimmune IgH rearrangement thr

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22

Perlmutter, R. M., B. Berson, J. A. Griffin, and L. Hood. "Diversity in the germline antibody repertoire. Molecular evolution of the T15 VN gene family." Journal of Experimental Medicine 162, no. 6 (1985): 1998–2016. http://dx.doi.org/10.1084/jem.162.6.1998.

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The T15 heavy chain variable region (VH) gene family in BALB/c mice includes four elements each greater than 88% homologous with the other. One of these elements, V1, encodes virtually all of the VH regions in BALB/c antiphosphorylcholine antibodies, while another element, V3, is a pseudogene and cannot be transcribed or translated. We have examined the structural features of this VH gene family in other mouse strains and, in particular, have cloned and sequenced the alleles of these gene segments present in B10.P mice. Each of the four B10.P sequences can be matched with its allelic counterpa

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23

Coutant, Frédéric, Jean-Jacques Pin, Florence Morfin-Sherpa, et al. "Impact of Host Immune Status on Discordant Anti-SARS-CoV-2 Circulating B Cell Frequencies and Antibody Levels." International Journal of Molecular Sciences 22, no. 20 (2021): 11095. http://dx.doi.org/10.3390/ijms222011095.

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Individuals with pre-existing chronic systemic low-grade inflammation are prone to develop severe COVID-19 and stronger anti-SARS-CoV-2 antibody responses. Whether this phenomenon reflects a differential expansion of antiviral B cells or a failure to regulate antibody synthesis remains unknown. Here, we compared the antiviral B cell repertoire of convalescent healthcare personnel to that of hospitalized patients with pre-existing comorbidities. Out of 277,500 immortalized B cell clones, antiviral B cell frequencies were determined by indirect immunofluorescence screening on SARS-CoV-2 infected

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Carlson, Chris, Eline Luning Prak, Jeanne Dagloria, et al. "Functional IGH V polymorphism is frequent in humans: implications for immunity and vaccination (HUM8P.349)." Journal of Immunology 192, no. 1_Supplement (2014): 185.24. http://dx.doi.org/10.4049/jimmunol.192.supp.185.24.

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Abstract Antibody heavy chain variable region genes (VH) are important for antigen binding, as evidenced by the dominant usage of particular VHs, such as the VH3b subfamily, in the immune responses to the capsular polysaccharide of H. influenza b. The presence or absence of particular VH alleles may be important for immunity. To screen for polymorphic VH alleles in humans, we sequenced functionally rearranged VH from 500K circulating B cells in each of 100 healthy young adults. We focused on the naïve repertoire (0-1 mutations compared to the closest known germline allele), and analyzed the pr

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Heeb, Silvan Rolf, Monica Schaller, and Johanna Anna Kremer Hovinga. "Anti-idiotypic network involved in restoring ADAMTS13 activity in immune-mediated thrombotic thrombocytopenic purpura (iTTP)." Journal of Immunology 204, no. 1_Supplement (2020): 224.29. http://dx.doi.org/10.4049/jimmunol.204.supp.224.29.

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Abstract The culprit of iTTP, a fatal autoimmune disease is a severe deficiency of the von Willebrand factor-cleaving protease ADAMTS13, caused by autoantibodies inhibiting its enzymatic activity. The pathophysiology upholding remission in certain patients but leading to relapse in others is unknown. We hypothesize that one mechanism keeping pathogenic autoantibodies in check is a network of anti-idiotypic antibodies, which we aimed to identify and characterize. From splenic mononuclear cells of two frequently relapsing iTTP patients (A and C), the anti-idiotypic IgG1 Fab κ/λ repertoire was am

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Bende, Richard J., Wilhelmina M. Aarts, Robert G. Riedl, Daphne de Jong, Steven T. Pals, and Carel J. M. van Noesel. "Among B cell non-Hodgkin's lymphomas, MALT lymphomas express a unique antibody repertoire with frequent rheumatoid factor reactivity." Journal of Experimental Medicine 201, no. 8 (2005): 1229–41. http://dx.doi.org/10.1084/jem.20050068.

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We analyzed the structure of antigen receptors of a comprehensive panel of mature B non-Hodgkin's lymphomas (B-NHLs) by comparing, at the amino acid level, their immunoglobulin (Ig)VH-CDR3s with CDR3 sequences present in GenBank. Follicular lymphomas, diffuse large B cell lymphomas, Burkitt's lymphomas, and myelomas expressed a CDR3 repertoire comparable to that of normal B cells. Mantle cell lymphomas and B cell chronic lymphocytic leukemias (B-CLLs) expressed clearly restricted albeit different CDR3 repertoires. Lymphomas of mucosa-associated lymphoid tissues (MALTs) were unique as 8 out of

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27

VanBlargan, Laura A., Leslie Goo, and Theodore C. Pierson. "Deconstructing the Antiviral Neutralizing-Antibody Response: Implications for Vaccine Development and Immunity." Microbiology and Molecular Biology Reviews 80, no. 4 (2016): 989–1010. http://dx.doi.org/10.1128/mmbr.00024-15.

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SUMMARYThe antibody response plays a key role in protection against viral infections. While antiviral antibodies may reduce the viral burden via several mechanisms, the ability to directly inhibit (neutralize) infection of cells has been extensively studied. Eliciting a neutralizing-antibody response is a goal of many vaccine development programs and commonly correlates with protection from disease. Considerable insights into the mechanisms of neutralization have been gained from studies of monoclonal antibodies, yet the individual contributions and dynamics of the repertoire of circulating an

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Lucas, Alexander H., and Donald C. Reason. "Aging and the Immune Response to theHaemophilus influenzae Type b Capsular Polysaccharide: Retention of the Dominant Idiotype and Antibody Function in the Elderly." Infection and Immunity 66, no. 4 (1998): 1752–54. http://dx.doi.org/10.1128/iai.66.4.1752-1754.1998.

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ABSTRACT Anti-Haemophilus influenzae b polysaccharide (Hib PS) antibodies elicited in elderly subjects following conjugate vaccination expressed a light-chain variable-region (VL)-associated idiotype and had functional activities similar to those previously observed in children and younger adults. These findings indicate that advanced age is not accompanied by shifts in the major VLcomponent of the Hib PS-specific repertoire or by diminution of the protective function of antibodies.

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Sesterhenn, Fabian, Che Yang, Jaume Bonet, et al. "De novo protein design enables the precise induction of RSV-neutralizing antibodies." Science 368, no. 6492 (2020): eaay5051. http://dx.doi.org/10.1126/science.aay5051.

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De novo protein design has been successful in expanding the natural protein repertoire. However, most de novo proteins lack biological function, presenting a major methodological challenge. In vaccinology, the induction of precise antibody responses remains a cornerstone for next-generation vaccines. Here, we present a protein design algorithm called TopoBuilder, with which we engineered epitope-focused immunogens displaying complex structural motifs. In both mice and nonhuman primates, cocktails of three de novo–designed immunogens induced robust neutralizing responses against the respiratory

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Haynes, Joel, Virginia Perry, Evelyn Benson, et al. "In Depth Breadth Analyses of Human Blockade Responses to Norovirus and Response to Vaccination." Viruses 11, no. 5 (2019): 392. http://dx.doi.org/10.3390/v11050392.

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To evaluate and understand the efficacy of vaccine candidates, supportive immunological measures are needed. Critical attributes for a norovirus vaccine are the strength and breadth of antibody responses against the many different genotypes. In the absence of suitable neutralization assays to test samples from vaccine clinical trials, blockade assays offer a method that can measure functional antibodies specific for many of the different norovirus strains. This paper describes development and optimization of blockade assays for an extended panel of 20 different norovirus strains that can provi

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Gajula, Kiran S., Peter J. Huwe, Charlie Y. Mo, et al. "High-throughput mutagenesis reveals functional determinants for DNA targeting by activation-induced deaminase." Nucleic Acids Research 42, no. 15 (2014): 9964–75. http://dx.doi.org/10.1093/nar/gku689.

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Abstract Antibody maturation is a critical immune process governed by the enzyme activation-induced deaminase (AID), a member of the AID/APOBEC DNA deaminase family. AID/APOBEC deaminases preferentially target cytosine within distinct preferred sequence motifs in DNA, with specificity largely conferred by a small 9–11 residue protein loop that differs among family members. Here, we aimed to determine the key functional characteristics of this protein loop in AID and to thereby inform our understanding of the mode of DNA engagement. To this end, we developed a methodology (Sat-Sel-Seq) that cou

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Ahmed, Rizwan, Zahra Omidian, Adebola Giwa, et al. "A newly discovered dual expresser lymphocyte that clonally expanded in Type 1 diabetes (T1D) patients secretes a public antibody that recognize public TCR in T1D." Journal of Immunology 204, no. 1_Supplement (2020): 142.10. http://dx.doi.org/10.4049/jimmunol.204.supp.142.10.

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Abstract PURPOSE We have recently discovered a new lymphocyte that co-express BCR and TCR (Ahmed et al, Cell, 2019: 177:11583) and referred as X cell to denote its crossover phenotype. Importantly, X cells express a public BCR that also encodes a potent autoantigen in its CDR3 sequence that is 10 fold more potent than native insulin peptide (InsB:9–23) in binding to DQ8 and activating autologous CD4 T cells. The x-autoantigen cross-activate insulin specific CD4 T cells as a peptide in the context of HLA-DQ8 molecules or as a soluble intact mAb (x-mAb). The goal of this study is to characterize

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Yawata, Makoto, Nobuyo Yawata, Monia Draghi, Ann-Margaret Little, Fotini Partheniou, and Peter Parham. "Roles for HLA and KIR polymorphisms in natural killer cell repertoire selection and modulation of effector function." Journal of Experimental Medicine 203, no. 3 (2006): 633–45. http://dx.doi.org/10.1084/jem.20051884.

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Interactions between killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands regulate the development and response of human natural killer (NK) cells. Natural selection drove an allele-level group A KIR haplotype and the HLA-C1 ligand to unusually high frequency in the Japanese, who provide a particularly informative population for investigating the mechanisms by which KIR and HLA polymorphism influence NK cell repertoire and function. HLA class I ligands increase the frequencies of NK cells expressing cognate KIR, an effect modified by gene dose, KIR

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Malkiel, Susan, Christopher Kuhlow, Patricio Mena, Gloria Monsalve, and Jorge Benach. "Mice with the Xid defect have impaired control against Borrelia burgdorferi infection but are more resistant to carditis (38.5)." Journal of Immunology 184, no. 1_Supplement (2010): 38.5. http://dx.doi.org/10.4049/jimmunol.184.supp.38.5.

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Abstract The antibody response is the main form of protection against Borrelia. Antibodies are functional in the elimination of the spirochetes and in resolution of disease. T cell-independent antibodies have been shown to have a protective role in defending the host against the Lyme disease spirochete B. burgdorferi. To determine the role of B1 cells in this antibody response, X-linked immunodeficient (Xid) CBA/N mice were used because they are severely deficient in B1 cells. Spirochete burdens were enhanced in the Xid mice compared to CBA/Ca controls at 3, 4 and 8 weeks postinfection, which

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Voss, William N., Yixuan J. Hou, Nicole V. Johnson, et al. "Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes." Science 372, no. 6546 (2021): 1108–12. http://dx.doi.org/10.1126/science.abg5268.

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The molecular composition and binding epitopes of the immunoglobulin G (IgG) antibodies that circulate in blood plasma after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are unknown. Proteomic deconvolution of the IgG repertoire to the spike glycoprotein in convalescent subjects revealed that the response is directed predominantly (>80%) against epitopes residing outside the receptor binding domain (RBD). In one subject, just four IgG lineages accounted for 93.5% of the response, including an amino (N)-terminal domain (NTD)–directed antibody that was protective aga

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Hughes, Darren L., Prachi Stafford, Samir W. Hamaia та ін. "Platelet integrin α2 I-domain specific antibodies produced via domain specific DNA vaccination combined with variable gene phage display". Thrombosis and Haemostasis 94, № 12 (2005): 1318–26. http://dx.doi.org/10.1160/th05-06-0410.

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SummaryAntibodies are a powerful tool for structure/function studies of platelet proteins. However, classic immunisation frequently elicits antibody responses against domains of minor functional interest. Robust strategies to generate antibodies against defined domains would be of significant interest in post-genome research. In this study, we report a new strategy using a combination of DNA vaccination and V gene phage display that allows the rapid generation of domain specific single-chain Fv antibodies (scFvs).This system was validated using the I-domain of α2 integrin as a model. The α2β1

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Zheng, Biao, Lei Fang, Qi Zhang, Wen Jiang, Shuhua Han, and Jun Qin. "Atg7 is critical for the functional maturation of germinal center B cells (LYM7P.625)." Journal of Immunology 194, no. 1_Supplement (2015): 200.17. http://dx.doi.org/10.4049/jimmunol.194.supp.200.17.

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Abstract The role of autophagy, especially individual components of the autophagy machinery, in antibody response has not been well established. Atg7 is an integral part in autophagesome formation and elongation. Using lineage- and stage-specific conditional knockout (CKO) mice, we have found that, in GC B cell-specific Atg7 CKO mice, although GC formation and structure were not affected by Atg7 deficiency, both primary and memory antibody responses were severely impaired in Atg7 CKO mice. Class-switch recombination (CSR) and Ig somatic hypermutation (SHM) were defective in Atg7-/- GC B-cells,

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Sherburn, Rebekah, William D. Tolbert, Suneetha Gottumukkala, Guillaume Beaudoin-Bussières, Andrés Finzi, and Marzena Pazgier. "Effects of gp120 Inner Domain (ID2) Immunogen Doses on Elicitation of Anti-HIV-1 Functional Fc-Effector Response to C1/C2 (Cluster A) Epitopes in Mice." Microorganisms 8, no. 10 (2020): 1490. http://dx.doi.org/10.3390/microorganisms8101490.

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Fc-mediated effector functions of antibodies, including antibody-dependent cytotoxicity (ADCC), have been shown to contribute to vaccine-induced protection from HIV-1 infection, especially those directed against non-neutralizing, CD4 inducible (CD4i) epitopes within the gp120 constant 1 and 2 regions (C1/C2 or Cluster A epitopes). However, recent passive immunization studies have not been able to definitively confirm roles for these antibodies in HIV-1 prevention mostly due to the complications of cross-species Fc–FcR interactions and suboptimal dosing strategies. Here, we use our stabilized g

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Kretschmer, Karsten, Anke Jungebloud, Jana Stopkowicz, Britta Stoermann, Reinhard Hoffmann, and Siegfried Weiss. "Antibody Repertoire and Gene Expression Profile: Implications for Different Developmental and Functional Traits of Splenic and Peritoneal B-1 Lymphocytes." Journal of Immunology 171, no. 3 (2003): 1192–201. http://dx.doi.org/10.4049/jimmunol.171.3.1192.

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Dale, Gordon A., Caitlin D. Bohannon, Daniel J. Wilkins, et al. "Gene conversion contributes significantly to IgHV somatic hypermutation in mice and humans." Journal of Immunology 198, no. 1_Supplement (2017): 195.7. http://dx.doi.org/10.4049/jimmunol.198.supp.195.7.

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Abstract During antigen-driven affinity maturation germinal center B lymphocytes undergo multiple rounds of somatic mutagenesis in the rearranged IgHV gene segment. A direct consequence of this process is the generation of multiple antibody mutants that are, in general, specific for antigen. Survival of these mutants is contingent on preserving or improving antigen-specificity in the complementarity-determining regions (CDRs) as well as retaining a functional framework region (FWR). Broadly, somatic mutations in germinal center B cells can be classified as templated or untemplated. In animals

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Pinschewer, Daniel D., Bénédict Fallet, Yi Hao, et al. "Chronic viral infection promotes efficient germinal center B cell responses." Journal of Immunology 204, no. 1_Supplement (2020): 247.4. http://dx.doi.org/10.4049/jimmunol.204.supp.247.4.

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Abstract Persistent viral infections subvert key elements of adaptive immunity. To compare germinal center (GC) B cell responses in chronic and acute lymphocytic choriomeningitis virus infection we exploit activation-induced deaminase (AID) fate-reporter mice and perform adoptive B cell transfer experiments. Chronic infection yields GC B cell responses of higher cellularity than acute infection, higher memory B cell and antibody secreting cell output for longer periods of time, a better representation of the late B cell repertoire in serum immunoglobulin and higher titers of protective neutral

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Fassò, Marcella, Niroshana Anandasabapathy, Frances Crawford, John Kappler, C. Garrison Fathman та William M. Ridgway. "T Cell Receptor (Tcr)-Mediated Repertoire Selection and Loss of Tcr Vβ Diversity during the Initiation of a Cd4+ T Cell Response in Vivo". Journal of Experimental Medicine 192, № 12 (2000): 1719–30. http://dx.doi.org/10.1084/jem.192.12.1719.

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We recently described a novel way to isolate populations of antigen-reactive CD4+ T cells with a wide range of reactivity to a specific antigen, using immunization with a fixed dose of nominal antigen and FACS® sorting by CD4high expression. Phenotypic, FACS®, functional, antibody inhibition, and major histocompatibility complex–peptide tetramer analyses, as well as T cell receptor Vβ sequence analyses, of the antigen-specific CD4high T cell populations demonstrated that a diverse sperm whale myoglobin 110–121–reactive CD4+ T cell repertoire was activated at the beginning (day 3 after immuniza

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Dzutsev, Amiran, Igor Belyakov, Dmitry Isakov, David Margulies, and Jay Berzofsky. "Avidity of CD8 T-cells sharpens immunodominance. (B9)." Journal of Immunology 178, no. 1_Supplement (2007): LB2. http://dx.doi.org/10.4049/jimmunol.178.supp.b9.

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Abstract In the course of viral infection, the immune system exploits only a fraction of the available CTL repertoire and focuses on a few of a myriad of potentially antigenic peptides. This phenomenon, known as immunodominance, depends on a number of factors, including antigen processing and transport, MHC binding, competition for antigen presenting cells, availability of the CD8 T-cell repertoire and other mechanisms that function largely by restricting the immune response. Here we elucidate a novel mechanism that increases the immunodominance of the epitope rather by enhancing the immune re

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Haire, R. N., R. D. Buell, R. T. Litman, et al. "Diversification, not use, of the immunoglobulin VH gene repertoire is restricted in DiGeorge syndrome." Journal of Experimental Medicine 178, no. 3 (1993): 825–34. http://dx.doi.org/10.1084/jem.178.3.825.

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Immunoglobulin (Ig) genes were isolated from unamplified conventional as well as polymerase chain reaction-generated cDNA libraries constructed from the peripheral blood cells of a patient with complete DiGeorge syndrome. Comparison of the sequences of 36 heavy chain clones to the recently expanded database of human VH genes permitted identification of the germline VH genes that are expressed in this patient as well as placement of 19 of these genes in a partially resolved 0.8-mb region of the human VH locus. The pattern of VH gene use does not resemble the fetal (early) repertoire. However, a

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Benedict, Cindy L., Susan Gilfillan, and John F. Kearney. "The Long Isoform of Terminal Deoxynucleotidyl Transferase Enters the Nucleus And, Rather than Catalyzing Nontemplated Nucleotide Addition, Modulates the Catalytic Activity of the Short Isoform." Journal of Experimental Medicine 193, no. 1 (2001): 89–100. http://dx.doi.org/10.1084/jem.193.1.89.

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During variable/diversity/joining (V[D]J) recombination, the enzyme terminal deoxynucleotidyl transferase (Tdt) adds random nucleotides at the junctions of the rearranging gene segments, increasing diversity of the antibody (Ab) and T cell receptor repertoires. Two splice variants of Tdt have been described, but only one (short isoform of Tdt [TdtS]) has been convincingly demonstrated to catalyze nontemplated (N) addition in vitro. We have expressed each splice variant of Tdt in transgenic (Tg) mice and found that the TdtS transgene catalyzes N addition on the endogenous Tdt−/− background and

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Prechl, József. "Network Organization of Antibody Interactions in Sequence and Structure Space: the RADARS Model." Antibodies 9, no. 2 (2020): 13. http://dx.doi.org/10.3390/antib9020013.

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Adaptive immunity in vertebrates is a complex self-organizing network of molecular interactions. While deep sequencing of the immune-receptor repertoire may reveal clonal relationships, functional interpretation of such data is hampered by the inherent limitations of converting sequence to structure to function. In this paper, a novel model of antibody interaction space and network, termed radial adjustment of system resolution, RAdial ADjustment of System Resolution (RADARS), is proposed. The model is based on the radial growth of interaction affinity of antibodies towards an infinity of dire

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Pasman, Yfke, and Azad Kaushik. "Elucidating the role of bovine heavy- and light-chain variable domains in polyspecific antigen-binding (P6104)." Journal of Immunology 190, no. 1_Supplement (2013): 141.15. http://dx.doi.org/10.4049/jimmunol.190.supp.141.15.

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Abstract The bovine antibody repertoire is generated from a limited germline sequence divergence as well as combinatorial diversity. Generation of an exceptionally long CDR3H (up to 61 amino acids) in the heavy chain variable region (VH) provides an additional mechanism to generate antibody diversity, not found in other species to date. These long CDR3H loops, present in polyspecific IgM, originate from VDJ recombination encoded by a specific VH gene, unusually long single DH-gene (capable of encoding up to 51 codons) and insertion of 15-18 base long conserved short nucleotide sequences (CSNS)

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Serpa, Jose A., Josemon Valayam, Daniel M. Musher, Roger D. Rossen, Liise-anne Pirofski, and Maria C. Rodriguez-Barradas. "VH3 Antibody Response to Immunization with Pneumococcal Polysaccharide Vaccine in Middle-Aged and Elderly Persons." Clinical and Vaccine Immunology 18, no. 3 (2011): 362–66. http://dx.doi.org/10.1128/cvi.00408-10.

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ABSTRACTPneumococcal disease continues to cause substantial morbidity and mortality among the elderly. Older adults may have high levels of anticapsular antibody after vaccination, but their antibodies show decreased functional activity. In addition, the protective effect of the pneumococcal polysaccharide vaccine (PPV) seems to cease as early as 3 to 5 years postvaccination. Recently, it was suggested that PPV elicits human antibodies that use predominantly VH3 gene segments and induce a repertoire shift with increased VH3 expression in peripheral B cells. Here we compared VH3-idiotypic antib

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Basu, Uttiya, Andrew Franklin, and Frederick W. Alt. "Post-translational regulation of activation-induced cytidine deaminase." Philosophical Transactions of the Royal Society B: Biological Sciences 364, no. 1517 (2008): 667–73. http://dx.doi.org/10.1098/rstb.2008.0194.

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The assembled immunoglobulin genes in the B cells of mice and humans are altered by distinct processes known as class switch recombination (CSR) and somatic hypermutation, leading to diversification of the antibody repertoire. These two DNA modification processes are initiated by the B cell-specific protein factor activation-induced cytidine deaminase (AID). AID is post-translationally modified by phosphorylation at multiple sites, although functional significance during CSR has been implicated only for phosphorylation at serine-38 (S38). Although multiple laboratories have demonstrated that A

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Panagides, Nadya, Lucia F. Zacchi, Mitchell J. De Souza, et al. "Evaluation of Phage Display Biopanning Strategies for the Selection of Anti-Cell Surface Receptor Antibodies." International Journal of Molecular Sciences 23, no. 15 (2022): 8470. http://dx.doi.org/10.3390/ijms23158470.

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Monoclonal antibodies (mAbs) are one of the most successful and versatile protein-based pharmaceutical products used to treat multiple pathological conditions. The remarkable specificity of mAbs and their affinity for biological targets has led to the implementation of mAbs in the therapeutic regime of oncogenic, chronic inflammatory, cardiovascular, and infectious diseases. Thus, the discovery of novel mAbs with defined functional activities is of crucial importance to expand our ability to address current and future clinical challenges. In vitro, antigen-driven affinity selection employing p

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