Enhanced T Cell Responses Due to Diacylglycerol Kinase Zeta Deficiency

Nat Immunol. 2003 Sep;4(9):882-90. doi: 10.1038/ni958. Epub 2003 Jul 27.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Cell Division / immunology
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism
  • Diacylglycerol Kinase / deficiency*
  • Diacylglycerol Kinase / immunology*
  • 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*

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • DNA-Binding Proteins
  • Guanine Nucleotide Exchange Factors
  • Lectins, C-Type
  • Phosphatidic Acids
  • Rasgrp1 protein, mouse
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2
  • Diacylglycerol Kinase