title: TCR affinity for thymoproteasome-dependent positively selecting peptides conditions antigen responsiveness in CD8(+) T cells.
abstract: In the thymus, low-affinity T cell antigen receptor (TCR) engagement facilitates positive selection of a useful T cell repertoire. Here we report that TCR responsiveness of mature CD8(+) T cells is fine tuned by their affinity for positively selecting peptides in the thymus and that optimal TCR responsiveness requires positive selection on major histocompatibility complex class I-associated peptides produced by the thymoproteasome, which is specifically expressed in the thymic cortical epithelium. Thymoproteasome-independent positive selection of monoclonal CD8(+) T cells results in aberrant TCR responsiveness, homeostatic maintenance and immune responses to infection. These results demonstrate a novel aspect of positive selection, in which TCR affinity for positively selecting peptides produced by thymic epithelium determines the subsequent antigen responsiveness of mature CD8(+) T cells in the periphery.
authors: Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima, Japan.
authors: Kensuke
authors: K
authors: Takada
authors: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors: Francois
authors: F
authors: Van Laethem
authors: Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
authors: Yan
authors: Y
authors: Xing
authors: Department of Immunology, Graduate School of Medicine, Nagoya University, Nagoya, Japan.
authors: Kazuyuki
authors: K
authors: Akane
authors: Department of Immunology, Graduate School of Medicine, Nagoya University, Nagoya, Japan.
authors: Haruhiko
authors: H
authors: Suzuki
authors: Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
authors: Shigeo
authors: http://orcid.org/0000-0002-3177-3503
authors: S
authors: Murata
authors: Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors: Keiji
authors: K
authors: Tanaka
authors: Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
authors: Stephen C
authors: SC
authors: Jameson
authors: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors: Alfred
authors: A
authors: Singer
authors: Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima, Japan.
authors: Yousuke
authors: Y
authors: Takahama
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D005434:Flow Cytometry; D051379:Mice; D010455:Peptides / Q000276:immunology; D046988:Proteasome Endopeptidase Complex / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013950:Thymus Gland / Q000201:enzymology
chemical_list: D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D046988:Proteasome Endopeptidase Complex