title: The tyrosine phosphatase PTPN22 discriminates weak self peptides from strong agonist TCR signals.
abstract: T cells must be tolerant of self antigens to avoid autoimmunity but responsive to foreign antigens to provide protection against infection. We found that in both naive T cells and effector T cells, the tyrosine phosphatase PTPN22 limited signaling via the T cell antigen receptor (TCR) by weak agonists and self antigens while not impeding responses to strong agonist antigens. T cells lacking PTPN22 showed enhanced formation of conjugates with antigen-presenting cells pulsed with weak peptides, which led to activation of the T cells and their production of inflammatory cytokines. This effect was exacerbated under conditions of lymphopenia, with the formation of potent memory T cells in the absence of PTPN22. Our data address how loss-of-function PTPN22 alleles can lead to the population expansion of effector and/or memory T cells and a predisposition to human autoimmunity.
authors.affiliation: Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, Ashworth Laboratories, The King's Buildings, University of Edinburgh, West Mains Road, Edinburgh, EH9 3JT, UK.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Salmond
authors.affiliation: Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, Ashworth Laboratories, The King's Buildings, University of Edinburgh, West Mains Road, Edinburgh, EH9 3JT, UK.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Brownlie
authors.affiliation: Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK.
authors.forename: Vicky L
authors.initials: VL
authors.lastname: Morrison
authors.affiliation: Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, Ashworth Laboratories, The King's Buildings, University of Edinburgh, West Mains Road, Edinburgh, EH9 3JT, UK.
authors.forename: Rose
authors.initials: R
authors.lastname: Zamoyska
mesh_terms: D000483:Alleles; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; C516766:Ptpn22 protein, mouse
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