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The Journal of Immunology, 2006, 176: 7502-7510.
Copyright © 2006 by The American Association of Immunologists

Protein Kinase C (PKC){alpha} and PKC{theta} Are the Major PKC Isotypes Involved in TCR Down-Regulation1

Marina von Essen*, Martin W. Nielsen*, Charlotte M. Bonefeld*, Lasse Boding*, Jeppe M. Larsen*, Michael Leitges{dagger}, Gottfried Baier{ddagger}, Niels Ødum* and Carsten Geisler2,*

* Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark; {dagger} Medical University, Hanover, Germany; and {ddagger} Department for Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria

It is well known that protein kinase C (PKC) plays an important role in regulation of TCR cell surface expression levels. However, eight different PKC isotypes are present in T cells, and to date the particular isotype(s) involved in TCR down-regulation remains to be identified. The aim of this study was to identify the PKC isotype(s) involved in TCR down-regulation and to elucidate the mechanism by which they induce TCR down-regulation. To accomplish this, we studied TCR down-regulation in the human T cell line Jurkat, in primary human T cells, or in the mouse T cell line DO11.10 in which we either overexpressed constitutive active or dominant-negative forms of various PKC isotypes. In addition, we studied TCR down-regulation in PKC knockout mice and by using small interfering RNA-mediated knockdown of specific PKC isotypes. We found that PKC{alpha} and PKC{theta} were the only PKC isotypes able to induce significant TCR down-regulation. Both isotypes mediated TCR down-regulation via the TCR recycling pathway that strictly depends on Ser126 and the di-leucine-based receptor-sorting motif of the CD3{gamma} chain. Finally, we found that PKC{theta} was mainly implicated in down-regulation of directly engaged TCR, whereas PKC{alpha} was involved in down-regulation of nonengaged TCR.


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The JI 2006 176: 7141-7142. [Full Text]  



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D. A. Alvarez-Arias and K. S. Campbell
Protein Kinase C Regulates Expression and Function of Inhibitory Killer Cell Ig-Like Receptors in NK Cells
J. Immunol., October 15, 2007; 179(8): 5281 - 5290.
[Abstract] [Full Text] [PDF]




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