title: 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 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.
authors.affiliation: Inserm, Nantes, France.
authors.forename: Leslie
authors.initials: L
authors.lastname: Hesnard
authors.affiliation: Inserm, Nantes, France.
authors.forename: François
authors.initials: F
authors.lastname: Legoux
authors.affiliation: Inserm, Nantes, France.|Université Nantes, Nantes, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Gautreau
authors.affiliation: Inserm, Nantes, France.
authors.forename: Melinda
authors.initials: M
authors.lastname: Moyon
authors.affiliation: Service de CTCV, Institut du Thorax, Nantes, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Baron
authors.affiliation: Inserm, Nantes, France.
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Devilder
authors.affiliation: Inserm, Nantes, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Bonneville
authors.affiliation: Inserm, Nantes, France.|Université Nantes, Nantes, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Saulquin
mesh_terms: D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D000939:Epitopes; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D060168:Thymocytes / Q000276:immunology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D001324:Autoantigens; D000939:Epitopes; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D010455:Peptides
keywords: Antigen · Human T cells · MHC · Tetramers · Thymocytes