title: The level of CD8 expression can determine the outcome of thymic selection.
abstract: During thymic development, thymocytes that can recognize major histocompatability complex (MHC) molecules on thymic epithelial cells are selected to survive and mature (positive selection), whereas thymocytes that recognize MHC on hematopoietic cells are destroyed (negative selection). It is not known how MHC recognition can mediate both death and survival. One model to explain this paradox proposes that thymocytes whose T cell antigen receptors (TCRs) recognize MHC with high affinity are eliminated by negative selection, whereas low affinity TCR-MHC interactions are sufficient to mediate positive selection. Here we report that, while the expression of a 2C TCR transgene leads to positive selection of thymocytes in H-2b mice, expression of both a CD8 transgene and a 2C TCR transgene causes negative selection. This observation indicates that quantitative differences in TCR-MHC recognition are a critical determinant of T cell fate, a finding predicted by the affinity model for thymic selection.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032.
authors.forename: E A
authors.initials: EA
authors.lastname: Robey
authors.forename: F
authors.initials: F
authors.lastname: Ramsdell
authors.forename: D
authors.initials: D
authors.lastname: Kioussis
authors.forename: W
authors.initials: W
authors.lastname: Sha
authors.forename: D
authors.initials: D
authors.lastname: Loh
authors.forename: R
authors.initials: R
authors.lastname: Axel
authors.forename: B J
authors.initials: BJ
authors.lastname: Fowlkes
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D015870:Gene Expression; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology*
chemical_list: D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell