Enhanced T cell responses due to diacylglycerol kinase ζ deficiency

• Published in: Nature immunology Vol. 4; no. 9; pp. 882 - 890
• Main Authors: Koretzky, Gary A, Zhong, Xiao-Ping, Hainey, Ehmonie A, Olenchock, Benjamin A, Jordan, Martha S, Maltzman, Jonathan S, Nichols, Kim E, Shen, Hao
• Format: Journal Article
• Language: English
• Published: United States 01-09-2003
• Subjects: Animals; Antigens, CD - immunology; Antigens, CD - metabolism; Antigens, Differentiation, T-Lymphocyte - immunology; Antigens, Differentiation, T-Lymphocyte - metabolism; Cell Division - immunology; Diacylglycerol Kinase - deficiency; Diacylglycerol Kinase - immunology; DNA-Binding Proteins - immunology; DNA-Binding Proteins - metabolism; Flow Cytometry; Guanine Nucleotide Exchange Factors; Immunoblotting; Lectins, C-Type; Lymphocyte Activation - immunology; Lymphocytic Choriomeningitis - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Phosphatidic Acids - immunology; Phosphatidic Acids - metabolism; Receptors, Antigen, T-Cell - immunology; Receptors, Interleukin-2 - immunology; Receptors, Interleukin-2 - metabolism; Signal Transduction - immunology; T-Lymphocytes - cytology; T-Lymphocytes - enzymology; T-Lymphocytes - immunology
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni958

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.