biostudies-literatureLesourne RIntramural NIH HHS1154-61https://www.ebi.ac.uk/biostudies/studies/S-EPMC3401357biostudies-literatureUnknown189(3)Themis1, a recently identified T cell protein, has a critical function in the generation of mature CD4(+)CD8(-) and CD4(-)CD8(+) (CD4 and CD8 single-positive [SP]) thymocytes and T cells. Although Themis1 has been shown to bind to the adaptor proteins LAT and Grb2, previous studies have yielded conflicting results regarding whether thymocytes from Themis1(-/-) mice exhibit TCR-mediated signaling defects. In this study, we demonstrate that, in the absence of Themis1, TCR-mediated signaling is selectively impaired in CD4 SP and CD8 SP thymocytes but is not affected in CD4(+)CD8(+) double-positive thymocytes despite high expression of Themis1 in double-positive thymocytes. Like Themis1, Themis2, a related member of the Themis family, which is expressed in B cells and macrophages, contains twoJournal of immunology (Baltimore, Md. : 1950)Interchangeability of Themis1 and Themis2 in thymocyte development reveals two related proteins with conserved molecular function.PMC3401357ZIA HD001803Barr VALesourne REl-Khoury DLove PEUehara SSong KDSamelson LEZvezdova EfalseInterchangeability of Themis1 and Themis2 in thymocyte development reveals two related proteins with conserved molecular function.Themis1, a recently identified T cell protein, has a critical function in the generation of mature CD4(+)CD8(-) and CD4(-)CD8(+) (CD4 and CD8 single-positive [SP]) thymocytes and T cells. Although Themis1 has been shown to bind to the adaptor proteins LAT and Grb2, previous studies have yielded conflicting results regarding whether thymocytes from Themis1(-/-) mice exhibit TCR-mediated signaling defects. In this study, we demonstrate that, in the absence of Themis1, TCR-mediated signaling is selectively impaired in CD4 SP and CD8 SP thymocytes but is not affected in CD4(+)CD8(+) double-positive thymocytes despite high expression of Themis1 in double-positive thymocytes. Like Themis1, Themis2, a related member of the Themis family, which is expressed in B cells and macrophages, contains two2012-01-01T00:00:00Z2012 Aug2026-04-07T16:38:38.218Z2019-03-27T00:55:48ZS-EPMC34013572273258810.4049/jimmunol.1200123