The tyrosine phosphatase PTPN22 discriminates weak self peptides from strong agonist TCR signals

Robert J. Salmond, Rebecca J. Brownlie, Vicky L. Morrison, Rose Zamoyska (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    69 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)875-883
    Number of pages8
    JournalNature Immunology
    Volume15
    Issue number9
    Early online date10 Aug 2014
    DOIs
    Publication statusPublished - Sep 2014

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