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

First Author  Salmond RJ Year  2014
Journal  Nat Immunol Volume  15
Issue  9 Pages  875-883
PubMed ID  25108421 Mgi Jnum  J:259368
Mgi Id  MGI:6142292 Doi  10.1038/ni.2958
Citation  Salmond RJ, et al. (2014) The tyrosine phosphatase PTPN22 discriminates weak self peptides from strong agonist TCR signals. Nat Immunol 15(9):875-883
abstractText  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.
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