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Trends Immunol. 2017 Sep;38(9):622-632. doi: 10.1016/j.it.2017.06.006. Epub 2017 Jul 8.

THEMIS: Two Models, Different Thresholds.

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, MD 20892, USA.
2
MRC Human Immunology Unit, Weatherall Institute for Molecular Medicine, Nuffield Department of Medicine, University of Oxford, Oxford OX3 9DS, UK.
3
Centre de Physiopathologie de Toulouse Purpan, Toulouse, France; 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 F-31300, France.
4
Section on Hematopoiesis and Lymphocyte Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: lovep@mail.nih.gov.

Abstract

THEMIS, a recently identified T-lineage-restricted protein, is the founding member of a large metazoan protein family. Gene inactivation studies have revealed a critical requirement for THEMIS during thymocyte positive selection, implicating THEMIS in signaling downstream of the T cell antigen receptor (TCR), but the mechanistic underpinnings of THEMIS function have remained elusive. A previous model posited that THEMIS prevents thymocytes from inappropriately crossing the positive/negative selection threshold by dampening TCR signaling. However, new data suggest an alternative model where THEMIS enhances TCR signaling enabling thymocytes to reach the threshold for positive selection, avoiding death by neglect. We review the data supporting each model and conclude that the preponderance of evidence favors an enhancing function for THEMIS in TCR signaling.

PMID:
28697966
PMCID:
PMC5788012
DOI:
10.1016/j.it.2017.06.006
[Indexed for MEDLINE]
Free PMC Article

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