Protein Kinase C 
Is Required for T Cell Activation and Homeostatic Proliferation
Guo Fu1*,
Jianfang Hu1
,
Nathalie Niederberger-Magnenat1,2
,
Vasily Rybakin1,
Javier Casas1,
Pia P. Yachi1
,
Stephanie Feldstein1||,
Bo Ma3,
John A. H. Hoerter1,
Jeanette Ampudia1,
Stephanie Rigaud1,
Florence Lambolez2,
Amanda L. Gavin1¶,
Karsten Sauer1,
Hilde Cheroutre2, and
Nicholas R. J. Gascoigne1*
1 Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
2 Department of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
3 Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
These authors contributed equally to this work.
Present address: Faculty of Biology and Medicine, University of Lausanne, CH-1011 Lausanne, Switzerland.
Present address: Applied Molecular Evolution, 3520 Dunhill Street, San Diego, CA 92121, USA.
|| Present address: School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
¶ Present address: Burnet Institute, 85 Commercial Road, Melbourne, Victoria 3004, Australia.
Abstract:
Protein kinase C 
(PKC) is abundant in T cells and is recruited to the immunological synapse that is formed between a T cell and an antigen-presenting cell; however, its function in T cells is unknown. We showed that PKC was required for the activation of mature CD8+ T cells through the T cell receptor. Compared with wild-type T cells, PKC–/– T cells showed poor proliferation in response to antigen stimulation, a trait shared with T cells deficient in PKC
, which is the most abundant PKC isoform in T cells and was thought to be the only PKC isoform with a specific role in T cell activation. In contrast, only PKC-deficient T cells showed defective homeostatic proliferation, which requires self-antigen recognition. PKC was dispensable for thymocyte development; however, thymocytes from mice doubly deficient in PKC and PKC exhibited poor development, indicating some redundancy between the PKC isoforms. Deficiency in PKC or PKC had opposing effects on the relative numbers of CD4+ and CD8+ T cells. PKC–/– mice had a higher ratio of CD4+ to CD8+ T cells compared to that of wild-type mice, whereas PKC–/– mice had a lower ratio. Mice deficient in both isoforms exhibited normal cell ratios. Together, these data suggest that PKC shares some redundant roles with PKC in T cell biology and also performs nonredundant functions that are required for T cell homeostasis and activation.
* To whom correspondence should be addressed. E-mail: gascoigne{at}scripps.edu (N.R.J.G.); guofu{at}scripps.edu (G.F.)
