T cell reactivity to MHC molecules: immunity versus tolerance.
The specificity of mature CD8+ and CD4+ T lymphocytes is controlled by major histocompatibility complex (MHC) class I and class II molecules, respectively. The MHC class specificity of T cells is stringent in many assays, but is less evident when cells are supplemented with exogenous lymphokines. The repertoire of T cells is shaped through contact with MHC molecules in the thymus and involves a complex process of positive selection and negative selection (tolerance). Tolerance of immature T cells to MHC molecules can reflect either clonal deletion or anergy and results from intrathymic contact with several cell types, including epithelial cells and cells with antigen-presenting function. Unlike immature T cells, mature T cells are relatively resistant to tolerance induction. In certain situations partial unresponsiveness of mature T cells can be achieved by exposing T cells to foreign MHC molecules expressed on atypical antigen-presenting cells. Tolerance is rarely complete, however, and the precise requirements for tolerizing mature T cells are still unclear.
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
J
J
Sprent
E K
EK
Gao
S R
SR
Webb
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D006649:Histocompatibility Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007108:Immune Tolerance; D007109:Immunity; D007376:Interleukin-2 / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
D000939:Epitopes; D006649:Histocompatibility Antigens; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell