Inefficient positive selection of T cells directed by haematopoietic cells.
Intrathymic differentiation of alpha beta TCR+ T cells depends on positive selection of CD4+CD8+ thymocytes by thymic major histocompatibility complex (MHC) molecules. Positive selection allows the maturation of only those T cells capable of restricted antigen recognition in the context of the hosts' MHC alleles. Studies of normal or T-cell receptor-transgenic mice engrafted with MHC-different bone marrow or thymuses support the conclusion that positive selection is directed by MHC molecules expressed on non-haematopoietic cells, presumably thymic epithelial cells. Here we, present contrary evidence that class I MHC molecules expressed by haematopoietic cell types direct positive selection of CD8+ T cells, though at a reduced rate compared with positive selection directed by thymic epithelial cells. The identity of cell types that direct positive selection bears directly on mechanistic models of the process, including the idea that thymic epithelial cell MHC molecules uniquely present specialized peptides that mediate positive selection, and the notion that thymic epithelial cells express unique differentiation-inducing cell surface molecules.
Bix
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Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Raulet
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D
D000818:Animals; D016827:CD8 Antigens / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D008099:Liver / Q000276:immunology; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D001613:beta 2-Microglobulin / Q000235:genetics
D016827:CD8 Antigens; D006183:H-2 Antigens; D011948:Receptors, Antigen, T-Cell; D001613:beta 2-Microglobulin