title: How the T cell repertoire becomes peptide and MHC specific.
abstract: T cells bearing alphabeta T cell receptors (TCRs) recognize antigens in the form of peptides bound to class I or class II major histocompatibility proteins (MHC). TCRs on mature T cells are usually very specific for both peptide and MHC class and allele. They are picked out from a precursor population in the thymus by MHC-driven positive and negative selection. Here we show that the pool of T cells initially positively selected in the thymus contains many T cells that are very crossreactive for peptide and MHC and that subsequent negative selection establishes the MHC-restriction and peptide specificity of peripheral T cells. Our results also suggest that germline-encoded TCR variable elements have an inherent predisposition to react with features shared by all MHC proteins.
authors.affiliation: Howard Hughes Medical Institute and Integrated Department of Immunology, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Huseby
authors.forename: Janice
authors.initials: J
authors.lastname: White
authors.forename: Frances
authors.initials: F
authors.lastname: Crawford
authors.forename: Tibor
authors.initials: T
authors.lastname: Vass
authors.forename: Dean
authors.initials: D
authors.lastname: Becker
authors.forename: Clemencia
authors.initials: C
authors.lastname: Pinilla
authors.forename: Philippa
authors.initials: P
authors.lastname: Marrack
authors.forename: John W
authors.initials: JW
authors.lastname: Kappler
mesh_terms: D000483:Alleles; D000818:Animals; D018095:Germ-Line Mutation; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018448:Models, Immunological; D008958:Models, Molecular; D010455:Peptides / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D037182:T-Cell Antigen Receptor Specificity; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta