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

Robert J. Salmond, Rebecca J. Brownlie, Vicky L. Morrison, Rose Zamoyska

Research output: Contribution to journalArticlepeer-review

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
JournalNature Immunology
Volume15
DOIs
Publication statusPublished - 10 Aug 2014

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