Preferential differentiation of T cell receptor specificities based on the MHC glycoproteins encountered during development. Evidence for positive selection.
T cells recognize foreign antigens together with those MHC glycoproteins they have encountered during their development in the thymus. How the repertoire of antigen-specific TCRs is selected has not yet been fully defined. We have investigated the T cell repertoire specificities of CD4-CD8+ cytotoxic T cells developing under conditions where one of the class I MHC-encoded molecules is blocked, while other class I-MHC glycoproteins are still expressed. We show that antigen-specific T cells restricted to the blocked class I fail to develop, while generation of other class I-specific T cell proceeds undisturbed. This highly selective perturbation of the T cell receptor repertoire demonstrates that development of CD4-CD8+ T cells with a certain TCR specificity requires expression of particular alleles of class I MHC. Thus, TCR-MHC interactions provide signals essential to the differentiation of precursor T cells.
Marusić-Galesić
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S
Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland 20892.
Longo
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DL
Kruisbeek
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AM
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D000911:Antibodies, Monoclonal; D002454:Cell Differentiation; D006023:Glycoproteins / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology*; D007116:Immunization, Passive; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000254:growth & development; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development; D014301:Trinitrobenzenes / Q000276:immunology
D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D011948:Receptors, Antigen, T-Cell; D014301:Trinitrobenzenes