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

Autor: Hesnard L; Inserm, Nantes, France., Legoux F; Inserm, Nantes, France., Gautreau L; Inserm, Nantes, France.; Université Nantes, Nantes, France., Moyon M; Inserm, Nantes, France., Baron O; Service de CTCV, Institut du Thorax, Nantes, France., Devilder MC; Inserm, Nantes, France., Bonneville M; Inserm, Nantes, France., Saulquin X; Inserm, Nantes, France.; Université Nantes, Nantes, France.
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2016 Mar; Vol. 46 (3), pp. 560-9. Date of Electronic Publication: 2015 Dec 22.
DOI: 10.1002/eji.201545951
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.
(© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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