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Article
Nature Immunology  4, 882 - 890 (2003)
Published online: 27 July 2003; | doi:10.1038/ni958

Enhanced T cell responses due to diacylglycerol kinase zeta deficiency

Xiao-Ping Zhong1, 2, Ehmonie A Hainey1, 3, Benjamin A Olenchock4, Martha S Jordan1, 3, Jonathan S Maltzman1, 5, Kim E Nichols1, 7, Hao Shen6 & Gary A Koretzky1, 3

1  The Signal Transduction Program, The Abramson Family Cancer Research Institute, Philadelphia, Pennsylvania 19104, USA.

2  Department of Cancer Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

3  Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

4  The Immunology Graduate Group, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

5  Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

6  Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

7  Division of Pediatric Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.

Correspondence should be addressed to Gary A Koretzky koretzky@mail.med.upenn.edu
Much is known about how T cell receptor (TCR) engagement leads to T cell activation; however, the mechanisms terminating TCR signaling remain less clear. Diacylglycerol, generated after TCR ligation, is essential in T cells. Its function must be controlled tightly to maintain normal T cell homeostasis. Previous studies have shown that diacylglycerol kinase zeta (DGKzeta), which converts diacylglycerol to phosphatidic acid, can inhibit TCR signaling. Here we show that DGKzeta-deficient T cells are hyperresponsive to TCR stimulation both ex vivo and in vivo. Furthermore, DGKzeta-deficient mice mounted a more robust immune response to lymphocytic choriomeningitis virus infection than did wild-type mice. These results demonstrate the importance of DGKzeta as a physiological negative regulator of TCR signaling and T cell activation.

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Nature Immunology
ISSN: 1529-2908
EISSN: 1529-2916
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