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

Salmond, R. J., Brownlie, R. J., Morrison, V. L. and Zamoyska, R. (2014) The tyrosine phosphatase PTPN22 discriminates weak self peptides from strong agonist TCR signals. Nature Immunology, 15(9), pp. 875-883. (doi: 10.1038/ni.2958) (PMID:25108421) (PMCID:PMC4148831)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Morrison, Dr Vicky
• Authors: Salmond, R. J., Brownlie, R. J., Morrison, V. L., and Zamoyska, R.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Nature Immunology
• Publisher: Nature Publishing Group
• ISSN: 1529-2908
• ISSN (Online): 1529-2916