title: Thymic selection generates a large T cell pool recognizing a self-peptide in humans.
abstract: The low frequency of self-peptide-specific T cells in the human preimmune repertoire has so far precluded their direct evaluation. Here, we report an unexpected high frequency of T cells specific for the self-antigen Melan-A/MART-1 in CD8 single-positive thymocytes from human histocompatibility leukocyte antigen-A2 healthy individuals, which is maintained in the peripheral blood of newborns and adults. Postthymic replicative history of Melan-A/MART-1-specific CD8 T cells was independently assessed by quantifying T cell receptor excision circles and telomere length ex vivo. We provide direct evidence that the large T cell pool specific for the self-antigen Melan-A/MART-1 is mostly generated by thymic output of a high number of precursors. This represents the only known naive self-peptide-specific T cell repertoire directly accessible in humans.
authors.affiliation: Division of Clinical Onco-Immunology, University Hospital (CHUV), 1011 Lausanne, Switzerland.
authors.forename: Alfred
authors.initials: A
authors.lastname: Zippelius
authors.forename: Mikaël J
authors.initials: MJ
authors.lastname: Pittet
authors.forename: Pascal
authors.initials: P
authors.lastname: Batard
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rufer
authors.forename: Magda
authors.initials: M
authors.lastname: de Smedt
authors.forename: Philippe
authors.initials: P
authors.lastname: Guillaume
authors.forename: Kim
authors.initials: K
authors.lastname: Ellefsen
authors.forename: Danila
authors.initials: D
authors.lastname: Valmori
authors.forename: Danielle
authors.initials: D
authors.lastname: Liénard
authors.forename: Jean
authors.initials: J
authors.lastname: Plum
authors.forename: H Robson
authors.initials: HR
authors.lastname: MacDonald
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Speiser
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Cerottini
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm; D001324:Autoantigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D007231:Infant, Newborn; D008213:Lymphocyte Activation; D058965:MART-1 Antigen; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology; D013234:Stem Cells / Q000166:cytology / Q000276:immunology; D016615:Telomere / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D001324:Autoantigens; D015789:HLA-A2 Antigen; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta