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Variation in the Cd3 zeta (Cd247) gene correlates with altered T cell activation and is associated with autoimmune diabetes.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics. Univ Copenhagen, Dept Dis Biol, Fac Life Sci, DK-1870 Copenhagen C, Denmark.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics. Univ Toronto, Dept Immunol, Toronto, ON, Canada.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
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2010 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 184, no 10, 5537-5544 p.Article in journal (Refereed) Published
Abstract [en]

Tuning of TCR-mediated activation was demonstrated to be critical for lineage fate in T cell development, as well as in the control of autoimmunity. In this study, we identify a novel diabetes susceptibility gene, Idd28, in the NOD mouse and provide evidence that Cd3zeta (Cd247) constitutes a prime candidate gene for this locus. Moreover, we show that the allele of the Cd3zeta gene expressed in NOD and DBA/2 mouse strains confers lower levels of T cell activation compared with the allele expressed by C57BL/6 (B6), BALB/c, and C3H/HeJ mice. These results support a model in which the development of autoimmune diabetes is dependent on a TCR signal mediated by a less-efficient NOD allele of the Cd3zeta gene.

Place, publisher, year, edition, pages
2010. Vol. 184, no 10, 5537-5544 p.
National Category
Immunology in the medical area
Research subject
Medicine
Identifiers
URN: urn:nbn:se:umu:diva-41762DOI: 10.4049/jimmunol.0904012ISI: 000277530700014PubMedID: 20400699OAI: oai:DiVA.org:umu-41762DiVA: diva2:407740
Available from: 2011-04-01 Created: 2011-04-01 Last updated: 2017-12-11Bibliographically approved

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Lundholm, MarieMayans, SofiaMotta, ViniciusLöfgren-Burström, AnnaHolmberg, Dan
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