title: CD45-mediated control of TCR tuning in naïve and memory CD8+T cells.
abstract: Continuous contact with self-major histocompatibility complex (MHC) ligands is essential for survival of naïve T cells but not memory cells. This surprising finding implies that T cell subsets may vary in their relative T-cell receptor (TCR) sensitivity. Here we show that in CD8+T cells TCR sensitivity correlates inversely with levels of CD5, a marker for strong self-MHC reactivity. We also show that TCR sensitivity is lower in memory CD8+T cells than naïve cells. In both situations, TCR hypo-responsiveness applies only to short-term TCR signalling events and not to proliferation, and correlates directly with increased expression of a phosphatase, CD45 and reciprocal decreased expression of activated LCK. Inhibition by high CD45 on CD8+T cells may protect against overt TCR auto-MHC reactivity, while enhanced sensitivity to cytokines ensures strong responses to foreign antigens.
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, Pohang 790-784, Korea.|Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Korea.|Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, Pohang 790-784, Korea.|Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
authors.forename: Hee-Ok
authors.initials: HO
authors.lastname: Kim
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, Pohang 790-784, Korea.|Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Korea.
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Ju
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, Pohang 790-784, Korea.|Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Korea.
authors.forename: Yoon-Chul
authors.initials: YC
authors.lastname: Kye
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, Pohang 790-784, Korea.|Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Korea.
authors.forename: Gil-Woo
authors.initials: GW
authors.lastname: Lee
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, Pohang 790-784, Korea.|Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Korea.
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Korea.
authors.forename: Cheol-Heui
authors.initials: CH
authors.lastname: Yun
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
authors.forename: Nunzio
authors.initials: N
authors.lastname: Bottini
authors.affiliation: Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
authors.forename: Kylie
authors.initials: K
authors.lastname: Webster
authors.affiliation: Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
authors.forename: Christopher C
authors.identifier: 0000-0001-5296-6155
authors.initials: CC
authors.lastname: Goodnow
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, Pohang 790-784, Korea.|Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Korea.|La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Surh
authors.affiliation: Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
authors.forename: Cecile
authors.initials: C
authors.lastname: King
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Korea.|Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sprent
mesh_terms: D000818:Animals; D018956:CD5 Antigens / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D007156:Immunologic Memory / Q000276:immunology*; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism
chemical_list: D018956:CD5 Antigens; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D017493:Leukocyte Common Antigens