Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, CD / immunology
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Antigens, CD / metabolism
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Antigens, Differentiation, T-Lymphocyte / immunology
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Antigens, Differentiation, T-Lymphocyte / metabolism
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Cell Division / immunology
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DNA-Binding Proteins / immunology
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DNA-Binding Proteins / metabolism
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Diacylglycerol Kinase / deficiency*
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Diacylglycerol Kinase / immunology*
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Flow Cytometry
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Guanine Nucleotide Exchange Factors*
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Immunoblotting
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Lectins, C-Type
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Lymphocyte Activation / immunology
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Lymphocytic Choriomeningitis / immunology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Phosphatidic Acids / immunology
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Phosphatidic Acids / metabolism
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Receptors, Antigen, T-Cell / immunology*
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Receptors, Interleukin-2 / immunology
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Receptors, Interleukin-2 / metabolism
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Signal Transduction / immunology
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T-Lymphocytes / cytology
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T-Lymphocytes / enzymology*
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T-Lymphocytes / immunology*
Substances
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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CD69 antigen
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DNA-Binding Proteins
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Guanine Nucleotide Exchange Factors
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Lectins, C-Type
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Phosphatidic Acids
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Rasgrp1 protein, mouse
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Receptors, Antigen, T-Cell
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Receptors, Interleukin-2
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Diacylglycerol Kinase