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

Autor: Hesnard, Leslie, Legoux, François, Gautreau, Laetitia, Moyon, Melinda, Baron, Olivier, Devilder, Marie‐Claire, Bonneville, Marc, Saulquin, Xavier
Zdroj: European Journal of Immunology; Mar2016, Vol. 46 Issue 3, p560-569, 10p
Abstrakt: In the thymus, a T-cell repertoire able to confer protection against infectious and noninfectious 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 maturation 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 thymocytes at different stages of human T-cell development should open new perspectives in the understanding of the human thymic selection process. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index