Enhanced T cell responses due to diacylglycerol kinase zeta deficiency.
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.
Zhong
Xiao-Ping
XP
The Signal Transduction Program, The Abramson Family Cancer Research Institute, Philadelphia, Pennsylvania 19104, USA.
Hainey
Ehmonie A
EA
Olenchock
Benjamin A
BA
Jordan
Martha S
MS
Maltzman
Jonathan S
JS
Nichols
Kim E
KE
Shen
Hao
H
Koretzky
Gary A
GA
D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism; D019852:Diacylglycerol Kinase / Q000172:deficiency* / Q000276:immunology*; D005434:Flow Cytometry; D020662:Guanine Nucleotide Exchange Factors; D015151:Immunoblotting; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010712:Phosphatidic Acids / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D004268:DNA-Binding Proteins; D019852:Diacylglycerol Kinase; D020662:Guanine Nucleotide Exchange Factors; D037181:Lectins, C-Type; D010712:Phosphatidic Acids; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D000099192:CD69 Antigens; C112278:Rasgrp1 protein, mouse