title: The TCR's sensitivity to self peptide-MHC dictates the ability of naive CD8(+) T cells to respond to foreign antigens.
abstract: The strength with which complexes of self peptide and major histocompatibility complex (MHC) proteins are recognized by the T cell antigen receptor (TCR) dictates the homeostasis of naive CD8(+) T cells, but its effect on reactivity to foreign antigens is controversial. As expression of the negative regulator CD5 correlates with self-recognition, we studied CD5(lo) and CD5(hi) naive CD8(+) T cells. Gene-expression characteristics suggested CD5(hi) cells were better poised for reactivity and differentiation than were CD5(lo) cells, and we found that the CD5(hi) pool also exhibited more efficient clonal recruitment and expansion, as well as enhanced reactivity to inflammatory cues, during the recognition of foreign antigen. However, the recognition of complexes of foreign peptide and MHC was similar for both subsets. Thus, CD8(+) T cells with higher self-reactivity dominate the immune response to foreign antigens, with implications for T cell repertoire diversity and autoimmunity.
authors.affiliation: Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: Ross B
authors.initials: RB
authors.lastname: Fulton
authors.affiliation: Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Hamilton
authors.affiliation: Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xing
authors.affiliation: Division of Biological Sciences, University of California San Diego, La Jolla, California, USA.
authors.forename: J Adam
authors.initials: JA
authors.lastname: Best
authors.affiliation: Division of Biological Sciences, University of California San Diego, La Jolla, California, USA.
authors.forename: Ananda W
authors.initials: AW
authors.lastname: Goldrath
authors.affiliation: Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Hogquist
authors.affiliation: Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Jameson
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D018956:CD5 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006706:Homeostasis / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms
chemical_list: D001324:Autoantigens; D018956:CD5 Antigens; C526836:Cd5 protein, mouse; D011948:Receptors, Antigen, T-Cell