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Role of the MHC restriction during maturation of antigen-specific human T cells in the thymus

Abstract : In the thymus, a T-cell repertoire able to confer protection against infectious and noninfec-tious agents in a peptide-dependent, self-MHC-restricted manner is selected. Direct detection of Ag-specific thymocytes, and analysis of the impact of the expression of the MHC-restricting allele on their frequency or function has never been studied in humans because of the extremely low precursor frequency. Here, we used a tetramer-based enrichment protocol to analyze the ex vivo frequency and activation-phenotype of human thymocytes specific for self, viral and tumor-antigens presented by HLA-A*0201 (A2) in individuals expressing or not this allele. Ag-specific thymocytes were quantified within both CD4CD8 double or single-positive compartments in every donor. Our data indicate that the mat-uration efficiency of Ag-specific thymocytes is poorly affected by HLA-A2 expression, in terms of frequencies. Nevertheless, A2-restricted T-cell lines from A2 + donors reacted to A2 + cell lines in a highly peptide-specific fashion, whereas their alloreactive counterparts showed off-target activity. This first ex vivo analysis of human antigen-specific thymo-cytes at different stages of human T-cell development should open new perspectives in the understanding of the human thymic selection process.
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Submitted on : Monday, April 20, 2020 - 11:29:55 AM
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Leslie Hesnard, François Legoux, Laetitia Gautreau, Melinda Moyon, Olivier Baron, et al.. Role of the MHC restriction during maturation of antigen-specific human T cells in the thymus. European Journal of Immunology, Wiley-VCH Verlag, 2016, 46, pp.560 - 569. ⟨10.1002/eji.201545951⟩. ⟨inserm-02547732⟩



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