Selecting T cell receptors with high affinity for self-MHC by decreasing the contribution of CD8.
Selective events during T cell repertoire development in the thymus include both the positive selection of cells whose receptors recognize self-major histocompatibility complex (MHC) molecules and negative selection (tolerance) of cells whose interaction with self-MHC is of high affinity. The affinity of T cell interactions with class I MHC molecules includes contributions by both the T cell receptor and the CD8 coreceptor. Therefore, by decreasing the affinity of the interaction with CD8, T cells whose receptors have relatively high affinities for self-MHC may survive negative selection. Such T cells were generated and those T cells reactive with self-MHC plus antigen also displayed low affinity for self.
Sherman
L A
LA
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
Hesse
S V
SV
Irwin
M J
MJ
La Face
D
D
Peterson
P
P
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology*; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D009980:Influenza A virus / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013950:Thymus Gland / Q000254:growth & development / Q000276:immunology
D000956:Antigens, Viral; D016827:CD8 Antigens; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell