How the T Cell Repertoire Becomes Peptide and MHC Specific

• Published in: Cell Vol. 122; no. 2; pp. 247 - 260
• Main Authors: Huseby, Eric S., White, Janice, Crawford, Frances, Vass, Tibor, Becker, Dean, Pinilla, Clemencia, Marrack, Philippa, Kappler, John W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.07.2005
• Subjects: Alleles; Animals; Germ-Line Mutation; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - immunology; Hybridomas - immunology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Models, Immunological; Models, Molecular; Peptides - immunology; Receptors, Antigen, T-Cell, alpha-beta - chemistry; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Antigen, T-Cell, alpha-beta - immunology; T-Cell Antigen Receptor Specificity; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Thymus Gland - cytology; Thymus Gland - immunology
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2005.05.013

T cells bearing αβ 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.