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Nat Immunol. 2017 Apr;18(4):433-441. doi: 10.1038/ni.3692. Epub 2017 Feb 27.

THEMIS enhances TCR signaling and enables positive selection by selective inhibition of the phosphatase SHP-1.

Author information

1
Section on Hematopoiesis and Lymphocyte Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
2
Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.
3
Institut National de la Santé et de la Recherche Médicale, U1043, Centre National de la Recherche Scientifique, U5282, and Université de Toulouse, Université Paul Sabatier, Toulouse, France.
4
National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA.

Abstract

THEMIS, a T cell-specific protein with high expression in CD4+CD8+ thymocytes, has a crucial role in positive selection and T cell development. THEMIS lacks defined catalytic domains but contains two tandem repeats of a distinctive module of unknown function (CABIT). Here we found that THEMIS directly regulated the catalytic activity of the tyrosine phosphatase SHP-1. This action was mediated by the CABIT modules, which bound to the phosphatase domain of SHP-1 and promoted or stabilized oxidation of SHP-1's catalytic cysteine residue, which inhibited the tyrosine-phosphatase activity of SHP-1. Deletion of SHP-1 alleviated the developmental block in Themis-/- thymocytes. Thus, THEMIS facilitates thymocyte positive selection by enhancing the T cell antigen receptor signaling response to low-affinity ligands.

PMID:
28250424
PMCID:
PMC5807080
DOI:
10.1038/ni.3692
[Indexed for MEDLINE]
Free PMC Article

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