title: Disruption of CD8-dependent negative and positive selection of thymocytes is correlated with a decreased association between CD8 and the protein tyrosine kinase, p56lck.
abstract: The CD4 and CD8 coreceptor molecules on immature thymocytes participate in T cell repertoire selection. To examine more definitively the role of CD4 and CD8 in the negative and positive selection of immature thymocytes, we generated transgenic mice with elevated surface CD4 expression and mated them with mice expressing a transgenic T cell receptor. Augmented CD4 expression was found to markedly alter CD8-dependent negative and positive selection of T cells specific for the male (H-Y) antigen presented by H-2Db major histocompatibility complex class I molecules. Moreover, the cytoplasmic tail of CD4 was essential for effecting these alterations, since the overexpression of tailless CD4 molecules failed to influence the outcome of CD8-dependent selection. The inhibition of positive and negative selection in double-transgenic mice expressing the full-length CD4 molecule was associated with a decreased interaction between the protein tyrosine kinase p56lck and CD8. These results strongly implicate p56lck in T cell repertoire selection.
authors.affiliation: Department of Microbiology, University of British Columbia, Vancouver, Canada.
authors.forename: N S
authors.initials: NS
authors.lastname: Van Oers
authors.forename: A M
authors.initials: AM
authors.lastname: Garvin
authors.forename: C B
authors.initials: CB
authors.lastname: Davis
authors.forename: K A
authors.initials: KA
authors.lastname: Forbush
authors.forename: D A
authors.initials: DA
authors.lastname: Carlow
authors.forename: D R
authors.initials: DR
authors.lastname: Littman
authors.forename: R M
authors.initials: RM
authors.lastname: Perlmutter
authors.forename: H S
authors.initials: HS
authors.lastname: Teh
mesh_terms: D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000032:analysis / Q000235:genetics; D016827:CD8 Antigens / Q000032:analysis / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)