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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.

SUBMITTER: Salmond RJ

PROVIDER: S-EPMC4148831 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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

Salmond Robert J RJ Brownlie Rebecca J RJ Morrison Vicky L VL Zamoyska Rose R

Nature immunology 20140810 9

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, wh ...[more]

PMID: 25108421

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