Salmond, RJ, Brownlie, RJ, Morrison, VL et al. (1 more author) (2014) The tyrosine phosphatase PTPN22 discriminates weak self peptides from strong agonist TCR signals. Nature Immunology, 15 (9). pp. 875-883. ISSN 1529-2916
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | Autoimmunity |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Oncology and Cancer Research - Labs (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 29 Jun 2016 15:49 |
Last Modified: | 29 Jun 2016 15:49 |
Published Version: | https://dx.doi.org/10.1038/ni.2958 |
Status: | Published |
Publisher: | Nature Publishing Group |
Identification Number: | 10.1038/ni.2958 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:101010 |