title: Disruption of T lymphocyte positive and negative selection in mice lacking the CD8 beta chain.
abstract: The CD4 and CD8 coreceptors have been shown to play significant roles in the differentiation and activation of helper and cytotoxic T lymphocytes (CTLs), respectively. Coordinate binding of coreceptor and T cell receptor (TCR) to the same major histocompatibility complex (MHC) molecule and coreceptor interaction with the tyrosine kinase p56lck are required for effective signaling. Whereas CD4 is a monomer, CD8 consists of either alpha alpha homodimers or alpha beta heterodimers. Signaling properties of CD8 have been ascribed to the alpha chain, which binds to both the MHC class I and to p56lck, respectively. To study CD8 beta specifically, we have generated mice defective in its expression. We observe a significant reduction in the numbers of CD8+ T cells, but these cells have normal CTL activity. By breeding CD8 beta null mice with animals expressing a class I-specific TCR transgene, we show that CD8 beta plays a significant role in both positive and negative selection of developing thymocytes.
authors.affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco 94143-0414.
authors.forename: M E
authors.initials: ME
authors.lastname: Crooks
authors.forename: D R
authors.initials: DR
authors.lastname: Littman
mesh_terms: D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D016827:CD8 Antigens / Q000235:genetics* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D017931:DNA Primers / Q000235:genetics; D005805:Genes, MHC Class I; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D016827:CD8 Antigens; D017931:DNA Primers; D011948:Receptors, Antigen, T-Cell