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Sci. Signal., 6 December 2011
Vol. 4, Issue 202, p. ra84
[DOI: 10.1126/scisignal.2002058]

RESEARCH ARTICLES

Protein Kinase C {eta} Is Required for T Cell Activation and Homeostatic Proliferation

Guo Fu1*, Jianfang Hu1{dagger}, Nathalie Niederberger-Magnenat1,2{dagger}{ddagger}, 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.

{dagger} These authors contributed equally to this work.

{ddagger} 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 {eta} (PKC{eta}) 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{eta} was required for the activation of mature CD8+ T cells through the T cell receptor. Compared with wild-type T cells, PKC{eta}–/– T cells showed poor proliferation in response to antigen stimulation, a trait shared with T cells deficient in PKC{theta}, 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{eta}-deficient T cells showed defective homeostatic proliferation, which requires self-antigen recognition. PKC{eta} was dispensable for thymocyte development; however, thymocytes from mice doubly deficient in PKC{eta} and PKC{theta} exhibited poor development, indicating some redundancy between the PKC isoforms. Deficiency in PKC{eta} or PKC{theta} had opposing effects on the relative numbers of CD4+ and CD8+ T cells. PKC{eta}–/– mice had a higher ratio of CD4+ to CD8+ T cells compared to that of wild-type mice, whereas PKC{theta}–/– mice had a lower ratio. Mice deficient in both isoforms exhibited normal cell ratios. Together, these data suggest that PKC{eta} shares some redundant roles with PKC{theta} 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.)

Citation: G. Fu, J. Hu, N. Niederberger-Magnenat, V. Rybakin, J. Casas, P. P. Yachi, S. Feldstein, B. Ma, J. A. H. Hoerter, J. Ampudia, S. Rigaud, F. Lambolez, A. L. Gavin, K. Sauer, H. Cheroutre, N. R. J. Gascoigne, Protein Kinase C {eta} Is Required for T Cell Activation and Homeostatic Proliferation. Sci. Signal. 4, ra84 (2011).

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