Article abstract
Nature Immunology 10, 831 - 839 (2009)
Published online: 13 July 2009 | Corrected online: 19 August 2009 | doi:10.1038/ni.1769
Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection
Andy L Johnson1,2, L Aravind3, Natalia Shulzhenko2, Andre Morgun2, See-Young Choi2, Tanya L Crockford1, Teresa Lambe1, Heather Domaschenz4, Edyta M Kucharska4, Lixin Zheng5, Carola G Vinuesa4, Michael J Lenardo5, Christopher C Goodnow4, Richard J Cornall1,6 & Ronald H Schwartz2,6
Abstract
T cell antigen receptor (TCR) signaling in CD4+CD8+ double-positive thymocytes determines cell survival and lineage commitment, but the genetic and molecular basis of this process is poorly defined. To address this issue, we used ethylnitrosourea mutagenesis to identify a previously unknown T lineage–specific gene, Themis, which is critical for the completion of positive selection. Themis contains a tandem repeat of a unique globular domain (called 'CABIT' here) that includes a cysteine motif that defines a family of five uncharacterized vertebrate proteins with orthologs in most animal species. Themis-deficient thymocytes showed no substantial impairment in early TCR signaling but did show altered expression of genes involved in the cell cycle and survival before and during positive selection. Our data suggest a unique function for Themis in sustaining positive selection.
- Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK.
- Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
- National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA.
- Australian Cancer Research Foundation Genetics Laboratory, John Curtin School of Medical Research, Australian National University, and Australian Phenomics Facility, Canberra, Australia.
- Laboratory of Immunology, National Institutes of Health, Bethesda, Maryland, USA.
- These authors contributed equally to this work.
Correspondence to: Richard J Cornall1,6 e-mail: richard.cornall@ndm.ox.ac.uk
Correspondence to: Ronald H Schwartz2,6 e-mail: rschwartz@niaid.nih.gov
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