Dissertations / Theses on the topic 'Antigènes T'
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Guillaume, Yves. "Caractérisation fonctionnelle de la molécule CD277 dans les lymhocytres T Vγ9Vδ2." Aix-Marseille 2, 2009. http://www.theses.fr/2009AIX20654.
Favre, Cédric. "Rôle de la molécule d'adhésion CD28 dans l'activation lymphocytaire T." Aix-Marseille 2, 2003. http://www.theses.fr/2003AIX22031.
Guirlinger, Marie-Joëlle. "Caractérisation immunochimique des antigènes excrétés-sécrétés par Toxoplasma gondii." Lyon 1, 1993. http://www.theses.fr/1993LYO10073.
Louveau, Antoine. "Rôle de la molécule adaptatrice CD3zeta et de la voie de co-stimulation CTLA4/CD80-CD86 dans le développement et la plasticité neuronale." Nantes, 2013. http://archive.bu.univ-nantes.fr/pollux/show.action?id=428743af-fa66-4821-8b8d-cd4e57adf2dd.
Recent studies have shown that molecules thought to be restricted to the immune system (IS) are expressed in the central nervous system (CNS) where they exert non-immune function on neuronal development and plasticity. We studied the cerebral function of the immunoreceptor CD3zeta and of the CTLA4/CD80-CD86 co-stimulatory pathway. Regarding CD3zeta, we found that CD3zeta inhibits neurite formation at early neuronal developmental stages, through a mechanism involving the ephrinA1/EphA4 pathway. In mature neurons, CD3zeta supports the synaptic localization of the NMDAR subunit GluN2A, and is required for the CaMKII-dependent signaling pathway underlying synaptic plasticity. These mechanisms are associated to a pro-cognitive action of CD3zeta on learning and memory behavior, independently of its immune role on T lymphocytes. Concerning the co-stimulatory pathway, we showed that the molecule CTLA4-Ig promotes axonal growth in vivo in a model of intracerebral transplantation. This effect is correlated with a morphological plasticity of microglial cells mediated through the microglial receptor CD86, and with an increased expression of BDNF and arginase 1. These results suggest that the beneficial effect of CTLA4-Ig on neuronal survival/growth is mediated through the release of microglial BDNF and arginase 1. Our studies reveal unexpected role of CD3zeta and the co-stimulatory molecules in the CNS. Our results highligt new mechanisms important to better understand neuroimmune interactions in normal and pathological conditions
Fornasa, Giulia. "Clivage du CD31 des lymphocytes T dans l'athérosclérose." Paris 7, 2011. http://www.theses.fr/2011PA077024.
Immune responses are controlled by inhibitory immune receptors such as CD31 that belongs to the family of Ig-like ITIM-containing receptors, ITIM for Immune receptor Tyrosine-based Inhibitory Motifs. The hemophilic engagement of the CD31 triggers the phosphorylation of the ITIM motifs leading to the inhibition of cellular activation pathways. During my thesis I have demonstrated that CD31 on T lymphocytes undergoes proteolytic cleavage upon cell activation. The concentration of the CD31 truncated soluble form released after cleavage in the circulation likely reflects the activation state of T lymphocytes. Indeed, it is higher in the plasma of patients with acute coronary syndromes and thus its measure could represent a potential novel diagnostic and prognostic tool for the evaluation of the cardiovascular disease risk. The homophilic engagement of CD31, and thus the inhibitory signaling, is disabled by the cleavage. However I demonstrated that an effective signal transmission can still occur targeting with a CD31-derived peptide the juxtamembrane portion, that remains expressed after the cleavage. The peptide, binding to its homotypic sequence on the truncated membrane-anchored fragment on T cells, restores the ITIM-dependent CD31 signalling and its inhibitory properties in vitro and in vivo. The administration of the CD31 peptide prevents experimental atherosclerosis development, inhibiting the pathologic immune responses favored by the CD31 cleavage on T cells. The CD31 peptide can be envisaged as a therapeutic tool to treat chronic inflammatory diseases characterized by massive lymphocytes activation
Davodeau, François. "Étude de la physiologie et du répertoire de reconnaissance des lymphocytes T [gamma delta] humains : contribution à l'étude des mécanismes générateurs de la diversité des récepteurs à l'antigène des lymphocytes T." Nantes, 1994. http://www.theses.fr/1994NANT12VS.
Harly, Christelle. "Modalités d’activation et fonctions des lymphocytes T gamma-delta humains." Nantes, 2011. http://archive.bu.univ-nantes.fr/pollux/show.action?id=1423324b-316e-46a1-b9c4-b4b7b772a246.
γdelta T lymphocytes (γdelta TL), stand in between innate and adaptative immunity. These lymphocytes are able to respond to various antigenic stimulations which reflects their potential implication in many infectious and tumoral physiopathological contexts. Fine activation modalities of these cells remain unclear, although their phenotypical and functional properties turn them potentially into pivotal players of the immune response. Understanding the modalities of activation of γdeltaTL currently represents an important issue for understanding the biology of these cells and evaluation of their therapeutical potential. The work achieved in this thesis is focused on the activation modalities of several humanγ deltaTL subsets, and leads to the identification of three major molecular players in these processes. (i) ILT2 expressed at the cell surface of B cell lines is essential for the activation of Vdelta2neg γdelta TL, (ii) EphA2 expressed by epithelial tumor cells is a key partner of Vdelta1pos γdeltaTL activation, (iii) expression of CD277 by target cells is mandatory for their specific recognition by Vdelta2pos γdeltaTL. However, the mecanisms implying these molecules in γdeltaTL activation processes remain still to be clearly defined and will be analyzed in further investigations. The expected results should lead to the evaluation of the role of these molecular and cellular players in vivo, along with their immunotherapeutical potential in various human pathologies
Huet, Stéphane. "Etude de l'activation lymphocytaire T par les molécules CD2 et CD3." Compiègne, 1988. http://www.theses.fr/1988COMPD125.
Human T lymphocyte activation by monoclonal antibodies (mAb) directed against CD2 or CD3 molecules required the presence of accessory cells (AC). It also appeared that the signal delivered to purify T-cells by different CD2 mAb pairs varied according to the CD2 pair used. Paraformaldehyde-fixed AC fully restored purified T-cells mitosis triggered by all CD2 pairs tested or by CD3 mAb. The required interaction between T-cells and AC involved CD18 molecules and HLA class I molecules from AC. In searching for the HLA class I counterpart from AC we found that both CD4+ and CD8+ cells responded to stimulation via CD2 and CD3. However, within the CD4 subsets, the CD4+ CD45R+ subset did not respond while the CD4+ CDw29+ did. Since the first subset is committed for the induction of suppression while the second to the induction of help, one can foresee how the immune response could develop in one direction or the other following the type of interaction that occurs during T-cell activation
Pepin, Elsa. "Étude des conséquences d'un stress hyperthermique sur l'appretement et la présentation des antigènes." Grenoble 1, 1998. http://www.theses.fr/1998GRE10042.
Espinosa, Carrasco Gabriel. "L'activation des cellules T CD8+ et T CD4+ en réponse aux auto-antigènes : du tissu lymphoïde à l'organe cible." Thesis, Montpellier, 2016. http://www.theses.fr/2016MONTT026.
The immune system has evolved multiple mechanisms of peripheral tolerance to control CD8+ T cell responses. Under particular conditions that are not yet well understood, potentially autoreactive T cells may override tolerance and differentiate into effector cells capable of targeting the own components of the organism resulting in self-reactivity. Utilizing transgenic mice expressing a model antigen in the beta cells of the pancreas, I have studied two important processes involved in CD8+ T cells differentiation in response to self-antigens. 1) Role of lipopolysaccharides (LPS) translocation in the breakdown of CD8+ T cell tolerance. It has been previously shown in our laboratory that lymphodepleting protocols, such as total body irradiation, promote breakdown of peripheral CD8+ T cell tolerance. Irradiation induces translocation of commensal bacteria LPS, a potent innate immune system activator, into the bloodstream. My data demonstrated that LPS translocation correlated with systemic activation of CD11c+ dendritic cells (DC), in particular CD8+ DC, responsible for pancreatic self-antigen cross-presentation, in lymphoid tissue. While antibiotic treatment of mice before irradiation prevented LPS translocation, DC activation was only partially affected, and onset of autoimmunity and breakdown of CD8+ T cell tolerance could not be prevented.2) Intra-vital visualization of effector CD8+ and CD4+ T cell cooperation in beta cell destruction in the pancreas. Using two-photon microscopy, I have been able, for the first time, to simultaneously analyze dynamics of fluorescently tagged autoreactive CD8+ and CD4+ T cells as they infiltrated the pancreas and induced autoimmune diabetes. I found that T cell infiltration promoted extracellular matrix remodeling in the pancreas, which in turn served as a scaffold for T cell migration. In addition, I showed that MHC class II dependent arrest of effector CD4+ T cells, due to interactions with antigen presenting cells, occasionally also implicating CD8+ T cells, provided help to effector CD8+ T cells in maintaining their effector functions
Le, Dréan Eric. "Contribution à l'étude fonctionnelle de clones de lymphocytes T spécifiques de mélanomes humains." Nantes, 1998. http://www.theses.fr/1998NANT2129.
Rouas-Freiss, Nathalie. "Présentation de l'antigène aux lymphocytes T : influence des phénomènes de capture de l'antigène." Paris 5, 1992. http://www.theses.fr/1992PA05P225.
Hommais, Valérie. "Présentation de l'antigène : données actuelles." Paris 5, 1990. http://www.theses.fr/1990PA05P134.
Brochu, Sylvie. "Tolérance et réponse des lymphocytes T aux antigènes mineurs d'histocompatibilité post-transplantation médullaire allogénique." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1995. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ32594.pdf.
M'homa, soudja Saïdi. "Phénoménologie de l'échappement tumoral dans un modèle murin de mélanome indictible." Aix-Marseille 2, 2009. http://www.theses.fr/2009AIX22078.
The role of the immune system in tumor progression is controversial. In studies of mouse transplanted tumors or spontaneous tumors expressing viral antigens, anti-tumor immune reactivity was found either to restrict or promote growth. We evaluated the impact of the immune system on two differencially aggressive melanomas developing in mice upon conditional deletion of the same tumor suppressor genes and concomitant expression of oncogene H-RasG12V and a natural cancer-germline tumor antigene. "Slow progressor" melanomas appeared to be "ignored" by the immune system. "Agressive" melanomas were infiltrated by immature myeloid cells and by T lymphocytes presenting an "exhausted" phenotype, in association with local inflammation and systemic Th2 dominant chronic inflammation. In constrast to other models, initiation of inflammation was here independent of adaptative immunity, which delayed the development of agressive melanomas, but was overridden by inflammation. In these mice, disorders in hematopoiesis and recuitment of myeloid cells to lymphoid organs were associated with immunosuppression and hampered adoptive T cell therapy. Expression of genes akin to those defining epithelial-mesenchymal transition as well as genes encoding chemokines and immuno-modulating cytokines characterized aggressive compared to slow progressor melomas, thus establishing a link between epithelial-mesenchymal transition-like processes and alterations of immune functions
Zini, Jean-Marc. "Le complexe majeur d'histocompatibilité humain : techniques d'études a propos d'un variant hla-dr7." Paris 7, 1989. http://www.theses.fr/1989PA072172.
Phothirath, Phoukham. "Génération de cellules T CD4+CD25+ suppressives induite par des lymphocytes T CD8+CD28- au cours de réactions leucocytaires mixtes autologues." Lyon 1, 2002. http://www.theses.fr/2002LYO1T195.
Magnusson, Fay. "Etude de la tolérance périphérique aux antigènes du soi dans un modèle de souris transgénique." Toulouse 3, 2008. http://thesesups.ups-tlse.fr/192/.
Several mechanisms of peripheral self-tolerance, including CD4+ CD25+ Foxp3+ regulatory T cells (Tregs), cross-presentation by dendritic cells (DCs) and the newly identified direct presentation of antigen by lymph node (LN) stromal cells, contribute to protecting our bodies and animals from self-damaging autoimmune diseases. We first sought to determine the relative contribution of antigen-specific CD8 and CD4 T cells to intestinal autoimmunity. To this end, we studied autoimmune targeting of an ectopic antigen expressed by enteric glial cells, in transgenic mouse models. We found that direct presentation of antigen by LN stromal cells caused the activation induced cell death of specific CD8 T cells. In contrast, conventional CD4 T cells were not affected by this mechanism of tolerance and their targeting of enteric glial cells produced lethal intestinal autoimmunity. Thus, we conclude that in our mouse model, this novel mechanism of peripheral tolerance preferentially protects against CD8 T cell intestinal autoimmunity. Furthermore, we have established a new model of antigen-specific CD4 T cell-mediated small intestine autoimmunity. To determine the relative contribution of Tregs, DCs and LN stromal cells for protection against autoimmunity, we sought conditions that make adoptively transferred naïve conventional CD8 T cells autoaggressive. Depletion of Treg cells, non-specific activation of the T cells through their lymphopenic expansion, and inhibition of TGF-beta receptor signaling in T cells achieved autoimmunity. The CD8 T cells caused multi-organ autoimmunity, but the intestine was not affected. Since insensitivity to TGF-beta rendered the T cells resistant to deletion through cross-presentation but not direct presentation of antigen, we conclude that the former was the critical mechanism determining the outcome of the immune response. Furthermore, these observations leave the possibility open that direct presentation by LN stromal cells preferentially protects the intestine against CD8 T cell attack, although other mechanisms of mucosal tolerance may be also involved. Altogether, these results provide new insights into the mechanisms of peripheral CD8 T cell tolerance, and tissue specific autoimmunity. A thorough understanding of these events is necessary to allow effective therapeutic intervention in autoimmunity and cancer
Lopez, Jodie. "Etude de l'impact du trafic intracellulaire et de la localisation des antigènes de Toxoplasma gondii sur leur présentation par les molécules du complexe d'histocompatibilité de classe I." Thesis, Toulouse 3, 2015. http://www.theses.fr/2015TOU30100/document.
CD8 T cells play a key role in protective immunity against intracellular pathogens such as Toxoplasma gondii (T. gondii) parasite. T. gondii resides inside host cell in parasitophorous vacuole. The host-T. gondii interface comprises a vacuole limiting membrane and a highly curved membraneous IntraVacuolar Network (IVN) of uncertain function. Many parasite effectors, including potential epitopes for CD8 T cells, are secreted by T. gondii to and across the boundary of their parasitophorous vacuole. Currently, the mechanisms controlling the targeting of parasite antigens to host cell are misunderstood et we don't kwnow how the intracellular transport of T. gondii proteins impacts on their access to MCH I pathway and their ability to induce CD8 T cell immunity. Using a multidisciplinary approach which combined reverse genetics in T. gondii, microscopy, antigen presentation measurements and in vivo experiments, I showed that insertion of a T. gondii dominant antigen at the vacuole limiting membrane is key for immunogenicity, yet that association of this antigen to high curvature IVN limits its presentation and curtails specific CD8 responses in mice. The IVN may play a role in immune modulation by limiting the access of parasite proteins to host cytosol and thus to MHC I pathway
Costello, Régis. "Activation des lymphocytes T humains par les anticorps monoclonaux dirigés contre les molécules CD2 et CD28." Aix-Marseille 2, 1993. http://www.theses.fr/1993AIX22061.
Brossay, Angélique. "Costimulation des lymphocytes T et différenciation dendritique des monocytes humains dans un modèle de présentation indirecte de xénoantigènes." Tours, 2002. http://www.theses.fr/2002TOUR3316.
We have previously demonstrated the presence of an indirect presentation pathway in a model based on the coculture of porcine aortic endothelial cells, human monocytes and T lymphocytes. In a simplified model without human monocytes, an anti-human CD2 monoclonal antibody blocked the lymphocyte proliferation suggesting that a porcine ortholog of human CD58 was expressed by porcine endothelial cells. We have cloned and sequenced the entire sequence of porcine CD58 and demonstrated that despite the expression of costimulatory molecules on endothelial cells, costimulatory signals were provided in cis by human monocytes. Next, we demonstrated that a monocyte-to-dendritic cell differentiation occur in this model. Dendritic cells obtained after a coculture human monocyte/porcine endothelial cells captured antigen, induced a lymphocyte proliferation and expressed the CCR7 receptor which favor migration toward lymphoid organs
Buaillon, Célia. "Etude des mécanismes moléculaires et cellulaires régulant la présentation des antigènes de Toxoplasma gondii par le CMH I." Thesis, Toulouse 3, 2016. http://www.theses.fr/2016TOU30321.
CD8 T lymphocytes play a major role for host protective immunity against intracellular parasites. CD8 T cells recognize antigens (Ag) presented by MHC I on the surface of antigen-presenting cells (APCs). Depending on the origin of Ag, two different processing and presentation pathways have been described: the classic one for endogenous and viral Ag, and the cross-presentation pathway for internalized exogenous Ag. Nevertheless, there are physiological conditions of exogenous Ag presentation by MHC I which do not fit any of these two pathways. It is the case for Toxoplasma gondii (T. gondii) infection. The mechanisms of processing in this infectious context are still unclear. T. gondii is an obligate intracellular parasite residing in a vacuole, a distinct compartment of a phagosome. Infection occurs via an active mechanism that induces the formation and maturation of parasitophorous vacuole (PV). Dense granule proteins (GRA) are a large parasite protein family, essential for the maturation of PV. GRA proteins are secreted as soluble proteins in the vacuole, and some are addressed to different membrane structures, such as the membrane intravacuolar network (IVN) and the vacuole limiting membrane (PVM). One of these GRA proteins (GRA6) is the source of an immunodominant epitope (HF10). Previous work highlighted in one dendritic cell line (DC), the role of SNARE Sec22b protein in membrane fusion between vesicles of the endoplasmic reticulum (ER) and the PV, and in the presentation of soluble Ova Ag, secreted by T. gondii. We have studied the role of Sec22b on Ag presentation of membrane-bound Ag (GRA6) in primary DC and macrophages by MHC I, using lentiviral transduction of shRNA. Our results confirmed the role of Sec22b on soluble Ag presentation in DC, which is not the case in macrophages. Finally, in DC and macrophages, we have shown that Sec22b does not impact on Ag presentation of membrane-bound Ags, such as GRA6. Besides this, our team highlighted that GRA6 is inserted in the PVM, with Cter exposed towards the host cell cytosol. Previously, our team published that effective presentation of the epitope derived from GRA6 requires its location at Cter of the protein. The association of these data prompted us to study the impact of Ag transmembrane topology on accessibility to MHC I processing and presentation. We developed a model to compare MHC I presentation of the HF10 epitope based on its exposition: at host cell cytosol, or, at vacuole lumen. Antigen presentation measurements by infected primary macrophages showed a decrease in HF10 presentation when exposed to the vacuole lumen side. My PhD work shed new light on the regulation of immunogenicity of T. gondii Ag at the cellular and molecular levels
Calin-Laurens, Véronique. "Étude de la présentation d'un antigène par les molécules du complexe majeur d'histocompatibilité de classe I et de classe II." Lyon 1, 1992. http://www.theses.fr/1992LYO1T174.
Duquesne, Véronique. "Étude du rôle fonctionnel des lymphocytes T dirigés contre des antigènes excrétés-sécrétés par Toxoplasma Gondii." Lille 1, 1990. http://www.theses.fr/1990LIL10029.
Rogel, Anne. "Caractérisation de réponses lymphocytaires T spécifiques de l'antigène de mélanome MELOE-1 chez les sujets sains et effet de la costimulation 4-1BB sur la survie des lymphocytes T CD8." Nantes, 2010. http://www.theses.fr/2010NANT39VS.
The injection of long peptides containing both CD8 and CD4 T cell epitopes is a promising approach for anti-tumor vaccination and the melanoma antigen MELOE-1 represents an interesting target for such immunotherapy strategies. We showed the existence of a MELOE-1 specific CD4 T cell repertoire in healthy donors and we identified two new CD4 epitopes, presented in distinct MHC-II molecules, next to the previously described CD8 epitope. Besides, we demonstrated that dendritic cells loaded with the MELOE-1 22-46 long peptide, including these three epitopes, could induce both CD8 and CD4 T cell responses. Finally, we studied the requirements for presentation of the different epitopes by dendritic cells. These results suggest that MELOE-1 22-46 represents an attractive candidate for the developpement of peptide vaccines in melanoma. In the second part of this work, we studied the effect of a recombinant form of the human 4-1BBL on CD8 T cell survival. The positive role of 4-1BB costimulation in the survival of these cells and the generation of memory cells, mainly via the increase of the anti-apoptotic protein Bcl-xL, has been well documented. Unexpectedely, we showed that in some stimulation conditions, 4-1BBL reduces Bcl-xL expression by CD8 T cells and that this effect seems to be restricted to naive cells. These results suggest a differential effect of this costimulation molecule on naive and memory CD8 T cells and must be taken account in therapeutic strategies based on 4-1BB costimulation
Fontenay, Michaëla. "Etude multiparamétrique de 60 cas de leucémies aigües myeloblastiques : identification d'une sous-population présentant un réarrangement de la chaine delta du récepteur T pour l'antigène." Paris 7, 1989. http://www.theses.fr/1989PA072171.
Meiffren, Grégory. "Rôles des groupes d'isoformes Cyt-1 et Cyt-2 de CD46 dans les réponses immunitaires : différenciation de lymphocytes T régulateurs et induction d'autophagie." Lyon, École normale supérieure (sciences), 2007. http://www.theses.fr/2007ENSL0432.
Lautrette, Christophe. "Etude du récepteur pro-apoptotique Fas dans des cellules neuronales et lymphocytaires T humaines." Limoges, 2003. http://www.theses.fr/2003LIMO0008.
This study is about the pro-apoptic Fas receptor in immune and central nervous systems. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with selective motor neuron death. About 26% of sera from ALS patients have elevated autoantibodies against the Fas protein with induced apoptosis by the Fas pathway in a human neuroblastic cell line and in rat motoneurons. Fas expression was detected in vivo and ex vivo in rat and human motoneurons. Cells from the neuroblastic cell line SH-SY5Y appeared heterogeneous. Cell separation by SdFFF based on size and density allowed us to obtain three populations with different differentiation stage. We have detected in the human T cell line Jurkat an extracellular phosphorylation of Fas 116 kDa aggregate by ectokinase C which inhibited Fas clustering at the cell membrane and apoptosis, suggesting a new extra-cellular regulation mechanism for the Fas pathway
Neveu, Raphaële. "Contribution à l'étude de la présentation des peptides synthétiques par les molécules du complexe majeur d'histocompatibilité de classe II." Lille 1, 2000. https://pepite-depot.univ-lille.fr/RESTREINT/Th_Num/2000/50376-2000-268.pdf.
Sur la base de cette hypothese, nous avons construit un peptide chimerique susceptible d'imposer une conformation differente de celle generee par le peptide natif. Nous avons ainsi revele que ces deux peptides generaient deux isoformes distinctes qui, bien que presentant le meme epitope, induisent in vivo des reponses cellulaires differentes. Par ailleurs, l'influence de la partie n-terminale sur la determination d'un motif d'ancrage du peptide clip naturel a ete evaluee. Nous avons ainsi identifie trois motifs potentiels d'interaction avec le sillon de fixation de dr1. D'autre part, nous avons tente de mettre au point un procede d'expertise biologique, base sur un protocole d'immunisation in vitro, permettant de valider des peptides a potentialite vaccinale. Dans son ensemble, ce travail contribue a une meilleure comprehension des mecanismes gouvernant l'interaction entre des peptides synthetiques et des molecules de cmh de classe ii
Le, Priol Yannick. "Du profil transcriptionnel à la caractérisation de la sous-population T CD8+CD57+ chez les patients infectés par le VIH et chez les individus séronégatifs." Paris 7, 2006. http://www.theses.fr/2006PA077127.
CD8+ T lymphocytes are main effector cells during the antiviral immune response. More than quantity, the quality of the cellular response mediated by CD8+ T lymphocytes is essential for an efficient immune response capable of controlling viral infections. Viral infections affect T cell homeostasis substantially and the lymphocyte compartment reaches a new state. In the case of an HIV infection, on top of CD4 T lymphocyte depletion, the proportion and the number of CD8 T lymphocytes increase. Differentiation pattern, migratory potencies and immune functions of CD8 T lymphocytes are modified. The CD8+CD57+ T lymphocyte subset, that is small in healthy individuels, is expanded when an HIV infection occurs and becomes a main CD8 T cell subset in the peripherical blood of HIV patients. The role of this T lymphocyte subset in the antiviral response remains almost unknown and controversial. In order to better characterised the CD8+CD57+ T cell subset we performed a transcriptome analysis of these cells issues from HIV-infected and -uninfected individuels. The transcriptome of CD8+CD57+ T cells remained unchanged in HIV patients compared to uninfected individuals. Transcriptional profiles of CD8+CD57+ and CD8+CD57- T cells were substantially distinct. The transcriptional signature of CD8+CD57+ T lymphocytes revealed cells with high effector cytotoxic potentiels (perforin, granzymes, granulysin) in HIV-infected and -uninfected individuals. CD8+CD57+ T lymphocytes are spécifie T cells for a large variety of antigens and produce large amounts of FN-alpha and TNF-gamma. The transcriptional profile of chemokine receptors and adhésion molecules suggests that these cells are destined to migrate to nonlymphoïd tissues. The main chemokine receptor expressed on them is CX3CR1. The mRNA expression profile of the molecules implicated in cell cycle processes show that CD8+CD57+ T cells have limited proliferation and survival capacities. These cells would be blocked in the G1 phase of the cell cycle and sensitive to caspase-dependant apoptosis. To conclude, this postgenomic approach allowed us to confer an identity to the CD8+CD57+ T cell subset. These cells have a high cytotoxic potential even if their migration, proliferation and survival potencies are limited. In HIV patients, the number and proportion of CD8+CD57+ T lymphocytes are increased and the quality of their antiviral response does not seem to be altered. The expansion of the CD8+CD57+ T cell subset reflects an activation of the immune System more than a skewed maturation of CD8+ T cells. The dilemma between their effector cytotoxic potentials and their homeostatic properties ask the question of their real capacity to confer an efficient immune protection
Lesport, Emilie. "Etude des mécanismes d'échappement des tumeurs aux cellules NK et T γδ induits par la molécule HLA-G." Paris 7, 2011. http://www.theses.fr/2011PA077043.
Natural Killer (NK) cells and γδ T cells are both cytotoxic effectors playing a major role in the immunosurveillance of cancers. Even though tumors can be eliminated thanks to the potent anti-tumoral fonctions of these immune cells, it is well establish that they develop various mechanisms in order to évade the immune System. In this regard, the aim of my thesis was to understand how the expression of the tolerogenic molécule HLA-G by tumor cells contributes to their escape from NK and γδ T cell recognition. We identified the molecular events leading to the inhibition of NK cell cytotoxicity induced by tumor cells expressing HLA-G. Our results demonstrate that the interaction of the ILT2 inhibitory receptor expressed by NK cells with HLA-G inhibits the reorganization of actin and tubulin cytoskeleton within the NK cells, thus preventing the polarization and the delivery of lytic granules toward the tumor target cells. In parallel, we studied the effect of HLA-G expression by tumor cells on the fonctions of γδ T cells. We showed that primary tumor cells expressing HLA-G are protected against γδ T cell-mediated cytolysis and that this inhibition was due to the interaction of HLA-G with ILT2. Moreover, our data indicate that HLA-G expression by tumor cells inhibits both the production of IFN-y and the proliferation of γδ T cells. Altogether, these results are important for a better understanding of the mechanisms linking HLA-G expression and tumor immune escape. In the future, they could contribute to the optimization of immunotherapy treatments for cancer patients expressing HLA-G
Ho, Wang Yin Kiave-Yune. "Mécanismes d'action de la molécule tolérogène HLA-G au travers de la trogocytose et détermination des structures de HLA-G fonctionnelles in vivo." Paris 7, 2010. http://www.theses.fr/2010PA077102.
HLA-G is a non-classical HLA class I molecule characterized by its tolerogenic properties. At the feto-maternal interface, HLA-G plays a key role in protecting the fetus against the immune System of the mother. The expression of HLA-G in allogeneic grafts is associated with better acceptance. Expressed by tumors, HLA-G endows them with a resistance to anti-tumor immunity. Understanding the cellular mechanisms and structures involved in the inhibitory fonctions of HLA-G is therefore a real therapeutic and diagnostic challenge. First, I studied the cellular mechanisms of inhibition by HLA-G mediated by trogocytosis and demonstrated that monocytes capture HLA-G 1 by trogocytosis from tumor cells. Unlike T lymphocytes and NK cells, monocytes that have captured HLA-G 1 do not behave as regulatory cells, but are able to transfer again HLA- Gl to other effectors (serial trogocytosis). I also showed that T cells are able to acquire the ILT2 receptor by trogocytosis from monocytes, which enables them to become sensitive to HLA-G 1. My second objective was to study the HLA-G structures that are functional in vivo. I demonstrated the existence of dimers of HLA-G2, G4 and G6, developed a detection method using ILT2 and ILT4 receptors, and determined the HLA-G structures recognized by these receptors. In particular, I demonstrated that thé ILT4 receptor recognizes the HLA-G6 isoform. Finally, T compared the efficiencies of HLA-G structures in vivo in a murine model of allogeneic skin graft
Bouziat, Romain. "Analyse des répertoires lymphocytaires T CD8+ murins éduqués par et mobilisés contre la molécule HLA-A02. 01." Paris 6, 2010. http://www.theses.fr/2010PA066267.
Iwaz, Jean. "Contrôle de la production des interleukines 1 et 2 et de l'expression des antigènes lymphocytaires par l'adénosine monophosphate cyclique." Lyon 1, 1990. http://www.theses.fr/1990LYO1T089.
Guillot, Cécile. "Étude chez le rat de l'expression localisée de molécules immunorégulatrices à l'aide de vecteurs adénoviraux : applications à la transplantation." Nantes, 2002. http://www.theses.fr/2002NANT03VS.
This thesis concerns the adenovirus-mediated gene transfer of immunosuppressive molecules to prolong allograft survival. Genetransfer of inhibitors of co-stimulatory T cells signal (such as CTLA4-Ig or CD40-Ig), or of immunosuppressive cytokines (such as TGFβ1), directly into the cardiac graft leads to a local production of immunosuppressives molecules that could create a microenvironment acting on the cells or molecules directly involved in graft recognition and destruction. Futhermore, little information is available concerning the effects of organ-localized overexpression of such immunosuppressive molecules. In this way, we have observed that intra-hepatic overexpression of IL-4 induces a lethal hepatitis, due to a direct pro-apoptotic effect of IL-4 on hepatocytes. .
Essaket, Soumia. "Alloréaction chez l'homme : spécificité de clones de lymphocytes T et structure primaire des molécules HLA-DR et HLA-DP." Toulouse 3, 1990. http://www.theses.fr/1990TOU30240.
Peigné, Cassie-Marie. "Modalités fines d'activation antigénique des LT Vγ9Vδ2 humains : mécanismes de détection du stress cellulaire et implication de la butyrophiline BTN3A/CD277." Nantes, 2016. https://archive.bu.univ-nantes.fr/pollux/show/show?id=f2d45559-cfa5-42ae-a547-6aaf17d1ae3c.
Vγ9Vδ2 T cells are the major sub-population of γδ T cells in human blood. They play a leading part in protection of the organism against infectious agents and tumor cells. Vγ9Vδ2 T cells are specifically and strongly activated by small organic pyrophosphate molecules termed phosphoantigens (PAg) in a TCR dependant way. PAg are metabolites from the isoprenoid pathway shared by both procaryotes and eucaryotes. The activation modalities of Vγ9Vδ2 T cells by PAg remain to be defined in detail. Results from our team revealed an important role played by the BTN3 (CD277) molecule during Vγ9Vδ2 T cell antigenic activation. BTN3, and especially the BTN3A1 isoform, is involved in activating Vγ9Vδ2 T cells. The work described in this thesis, aimed at investigating the underlying mechnisms allowing BTN3 molecule to activate Vγ9Vδ2 T cells. We showed that the B30. 2 intracellular domain of BTN3A1 was able to fix PAg with a histidine residue in position 351 playing a vital role. Furthermore, we identified other proteins that could interact with this intracellular domain. We used the yeast double-hybrid technique, and identified six putative partner proteins. Finally, we carried out a function maping of the intracellular part of the various BTN3 isoforms. These results brought new insights into the antigenic activation modalities of Vγ9Vδ2 T cells by PAg and clarify the key role played by the BTN3 molecule in this process
Hage, Faten El. "Identification d'un épitope tumoral partagé codé par le gène "calca" et réactivité lymphocytaire T dans un modèle de carcinome bronchique humain." Paris 12, 2007. http://www.theses.fr/2007PA120019.
We have identified a tumor antigen (AG) recognized on a human lung carcinoma by an autologous cytotoxic T cell clone. It is encoded by "calca" gene (calcitonin/calcitonin-gene-related peptide) which is overexpresses in a large range of lung cancers and medullary thyroïd carcinomas (MTC) but not in normal tissues. The epiptode derives from the signal peptide of the preprocalcitonin. Its processing is proteasome-and TAP-independent but involves the signal peptidase (SP) and the signal peptide peptidase (SPP). This antigenic peptide corresponds to a promising candidate for MTC and lung cancer immunotherapy. We have also studied the spontaneous T cell response generated against a tumor AG encoded by mutated A-actinin-4-gene. Our results indicated that T cell clones derivated from lymphocytes infiltrating the tumor lyse more efficiently the autologous tumor cells than those isolated from patient peripheral blood lymphocytes. The TCR inhibitory protein CD5 plays a critical role in modulating anti-tumor T cell response and in protecting peripheral blood T lymphocytes from activated induced cell death (AICD)
Godefroy, Emmanuelle. "La présentation croisée de la métalloprotéase matricielle-2 par les cellules de mélanome génère un épitope T spécifique de ce cancer." Nantes, 2004. http://www.theses.fr/2004NANT2077.
Most tumor cells express antigens that can be recognized by cytotoxic T CD8 lymphocytes. Nevertheless, immunotherapeutic trials, targeting various human tumor cell antigens recognized by T lymphocytes, have shown limited efficacy. To improve these treatments, it is necessary to identify new tumor antigens. With this aim, we studied the specificity of melanoma infiltrating lymphocytes from 22 patients. This screening allowed us to identify a new tumor antigen recognized by a CD8 T cell clone in the HLA-A*0201 context : the matrix metalloproteinase-2 (MMP-2). We also showed that the MMP-2560-568 epitope is not processed by the classical endogenous pathway, but by cross-presentation. The original processing of the MMP-2 epitope, only used by melanoma cells, and the pro-tumoral functions of MMP-2 make of this new antigen an ideal target for immunotherapy, and opens the way to new innovative therapeutic strategies to treat HLA-A*0201 melanoma patients
Bénéteau, Marie. "La modulation de l'apoptose dépendante du récepteur Fas : étude des évènements précoces de la voie de signalisation apoptotique dans un modèle de lymphocytes T humains." Bordeaux 2, 2006. http://www.theses.fr/2006BOR21328.
Fas belongs to the TNF-R superfamily and contains a death domain (DD) which behaves as a platform to launch the apoptotic signal. 1) Several reports described the appearance of high molecular mass forms of Fas which resist to denaturing and reducing conditions. We demonstrated that these microaggregates only appear upon agonistic anti-Fas antibody stimulus and do not play any role in the apoptotic signal. 2) Point mutations inside the Fas DD are responsible for the ALPS syndrome and have been described in various cancers. We selected T lymphocytes resistant to antibody-induced death but still sensitive to FasL treatment. A mutation into the Fas DD (Q257K) was responsible for this inhibition. We showed that the specific down-regulation of c-FLIP restored the Fas-mediated signal in these mutated cells. 3) Fas relocalization into the lipid rafts have been reported to increase the apoptotic signal. We observed that the P13K signaling pathway maintains Fas excluded from the lipid rafts
Soula-Rothhut, Mahdhia. "Etude de la phosphorylation de la P56Ick et détection des sites de phosphorylation par les voies de signalisation CD4 et TcR/CD3 dans les cellules T." Paris 7, 1993. http://www.theses.fr/1993PA077343.
Hudrisier, Denis. "Structure, fonction et pharmacologie des antigènes présentés par le complexe majeur d'histocompatibilité de classe I aux lymphocytes T cytotoxiques : étude des antigènes du virus de la chorioméningite lymphocytaire H-2Db-restreints." Toulouse 3, 1996. http://www.theses.fr/1996TOU30120.
Vidal, Karine. "Expression et propriétés fonctionnelles des produits de classe II du complexe majeur d'histocompatibilité sur les cellules épithéliales intestinales de souris." Lyon 1, 1993. http://www.theses.fr/1993LYO1T110.
Cornet, Sébastien. "Optimisation de la réponse immunitaire dirigée contre les antigènes de tumeurs universels : de la recherche au développement clinique." Paris 6, 2005. http://www.theses.fr/2005PA066283.
Pereira, Mathias. "Caractérisation des mécanismes de présentation des antigènes par les molécules du CMH-II." Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS293.
CD4+ helper T cells that orchestrate adaptive immune responses recognize antigen (Ag)-derived peptides presented by MHC-II molecules. MHC-II molecules are expressed by professional Ag- presenting cells (APCs) such as B cells and dendritic cells, thymic epithelial cells, and also by non-professional APCs in inflammatory conditions. MHC-II molecules present peptides derived from extra- and intra-cellular sources of Ags (endogenous). Ags are then delivered to the MIIC where they are progressively degraded by lysosomal proteases into peptides that can be loaded on MHC-II molecules. The pathways leading to endogenous Ag presentation by MHC-II molecules are poorly characterized. Macroautophagy has been shown to contribute to the processing of cytoplasmic and nuclear Ags for the loading of MHC-II molecules. Several forms of selective autophagy exist, but all rely on proteins named autophagy receptors (AR): p62, NBR1, NDP52, OPTN, and TAX1BP1 (T6BP). In addition to their role on selective autophagy, some of the ARs are also required for autophagosomes and endosomes maturation. We hypothesized that ARs could contribute at various levels to MHC-II-restricted viral Ag presentation. This work unravels a new role for T6BP, but not the others ARs, as a key player in MHC-II-restricted Ag presentation, and in CD4+ T cell immunity
Laffont, Sophie. "Rôle des lymphocytes cytotoxiques T CD8 et NK dans le contrôle des réponses T CD4 alloréactives." Toulouse 3, 2007. http://www.theses.fr/2007TOU30033.
CD4 T cells play an essential in allograft rejection. However, factors influencing their polarization into Th1 or Th2 effector cells in vivo are still poorly understood. We report here that in absence of CD8 T cell and/or NK cell activation, a strong CD4 T cells occurs characterized by the development of type-2 cytokine producing cells. In this situation, allogeneic skin grafts are heavily infiltrated with eosinophil. The aim of the study here was to investigate the mechanisms by which CD8 T lymphocytes and NK cells can control CD4 T cell priming. We found that, they both act by limiting the accumulation of donor-derived dendritic (Dcs) cells through a perforin-dependent mechanism. We propose that CD8 T cells and NK cells, by controlling the half-life of allogeneic DCs, modify the kinetics of DC differentiation in lymph nodes thereby modulate the amplitude and the polarization of alloreactive CD4 T cells
Chaperot, Laurence. "Étude de l'immunogénicité des cellules B malignes de lymphomes : application à la génération de lymphocytes T cytotoxiques antitumoraux." Université Joseph Fourier (Grenoble), 1996. http://www.theses.fr/1996GRE19010.
Brodovitch, Alexandre. "Détection et première analyse d'antigènes par les lymphocytes T." Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM4050/document.
T lymphocytes need to efficiently probe a large number of antigen-presenting cell (APC) in order to detect an agonist antigen and to initiate an effective immune response. Therefore, engagement of the T-cell receptor (TCR) by peptide-bound major histocompatibility complex (pMHC) is a highly sensitive and rapid process. While signaling pathways downstream the TCR are extensively studied, little is known about antigen discrimination kinetic and initial T-cell response.Model planar surfaces coated with TCR ligand allowed us to study cellular events initiated by antigen detection. Using TIRFM (total internal reflexion microscopy) and IRM (interference reflexion microscopy) we showed that T-cell initial contacts with the surface were mediated by mobile microvilli. TCR engagement triggers a pulling motion of T cell surface microvilli within seconds. Active microvilli movements are dependent on PLC-γ1 activation and on the presence of myosins (IIA, Ic and Ig) as well as cofilin and ezrin. After this extracellular environment probing period, TCR stimulation triggered a rapid and active cell spreading. Cell spreading amplitude and speed reflect the ligand activating efficacity. In less than 5 minutes pMHC with different biophysical properties were discriminated by T-cells and triggered a first specific cellular response
Rouleau, Matthieu. "Apoptose de lymphocytes T matures humains induite à travers la structure CD2." Compiègne, 1993. http://www.theses.fr/1993COMPD659.
Fauquembergue, Emilie. "Nouvelles stratégies d'immunothérapie cellulaire adoptive anti-tumorale basée sur l'activation de lymphocytes T cytotoxiques spécifiques : application aux cancers colorectaux." Rouen, 2012. http://www.theses.fr/2010ROUENR08.
Adoptive immunotherapy, based on in vitro tumor antigen-specific cytotoxic T cell (CTL) activation and expansion, is a promising approach for cancer treatment. In this context, we used a strategy based on peripheral T cell activation with artificial antigen presenting cells (AAPC). To apply this strategy to colorectal cancer, that have a high mortality, the aim of this work was to select and assess the ability of various antigens to induce a specific cytotoxic response in HLA-A*0201 context. First, we were interested by carcinoembryonic antigen (CEA), a potential target for immunotherapy because of its frequent overexpression in human carcinoma. We show that CAP1, a HLA-A*0201-restricted CEA-derived peptide, was not efficiently presented by tumor cell and that CEA, regardless of the epitope, is flot an appropriate target for T cell-based immunotherapy, in the HLA-A*0201 context. The potential role of tolerance mechanisms in this absence of response, led us ta study neoantigens, for which less tolerance mechanisms are expected, in colorectal cancer with microsatellite instability due ta a repair defect of DNA and characterized by a high immune infiltrate and a botter prognosis. In order ta characterize the frameshift mutations inducing a cytotoxic T cell response in these tumors, we analyzed in 80 CRC MSI+ the frequency of frameshift mutation of 19 target genes by fluorescent multiplex PCR comparative analysis. The four most frequently mutated genes was ACVR2 (90,9%), TAF1B (83,5%), ASTE1/HT001 (80,2%) and TGFBR2 (78,2%). We correlated the presence of these mutations with infiltrating T cell rate (CD3 and CD8) in tumors and we have shown that this rate was associated with the presence of frameshift mutations within three target genes: ASTE1MT001 and PTEN (CD3 and CD8) and BAX (CD8). These results argue for the evaluation of these antigens in our system of AAPC