title: Regulation of lineage commitment distinct from positive selection.
abstract: Developing alphabeta T cells diverge into the CD4 and CD8 lineages as they mature in the thymus. It is unclear whether lineage commitment is mechanistically distinct from the process that selects for the survival of T cells with useful T cell receptor (TCR) specificities (positive selection). In HD mice, which lack mature CD4+ T cells, major histocompatibility complex (MHC) class II-restricted T cells are redirected to the CD8 lineage independent of MHC class I expression. However, neither TCR-mediated signaling nor positive selection is impaired. Thus, the HD mutation provides genetic evidence that lineage commitment may be mechanistically distinct from positive selection.
authors.affiliation: Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA.
authors.forename: R
authors.initials: R
authors.lastname: Keefe
authors.forename: V
authors.initials: V
authors.lastname: Dave
authors.forename: D
authors.initials: D
authors.lastname: Allman
authors.forename: D
authors.initials: D
authors.lastname: Wiest
authors.forename: D J
authors.initials: DJ
authors.lastname: Kappes
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation; D019070:Cell Lineage; D003433:Crosses, Genetic; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010641:Phenotype; D010766:Phosphorylation; D011828:Radiation Chimera; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta