Role of the MHC restriction during maturation of antigen specific human T cells in the thymus
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.
European journal of immunology