Protein kinase C (PKC) alpha and PKC theta are the major PKC isotypes involved in TCR down-regulation

J Immunol. 2006 Jun 15;176(12):7502-10. doi: 10.4049/jimmunol.176.12.7502.


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 PKCalpha and PKCtheta 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 Ser(126) and the di-leucine-based receptor-sorting motif of the CD3gamma chain. Finally, we found that PKCtheta was mainly implicated in down-regulation of directly engaged TCR, whereas PKCalpha was involved in down-regulation of nonengaged TCR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Animals
  • CD3 Complex / physiology
  • Cell Line, Tumor
  • Cells, Cultured
  • Down-Regulation / genetics
  • Down-Regulation / immunology*
  • Humans
  • Hybridomas
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / deficiency
  • Isoenzymes / genetics
  • Isoenzymes / physiology*
  • Jurkat Cells
  • Leucine / metabolism
  • Mice
  • Mice, Knockout
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / deficiency
  • Protein Kinase C / genetics
  • Protein Kinase C / physiology*
  • Protein Kinase C-alpha / deficiency
  • Protein Kinase C-alpha / genetics
  • Protein Kinase C-alpha / physiology*
  • Protein Kinase C-theta
  • RNA, Small Interfering / pharmacology
  • Receptors, Antigen, T-Cell / antagonists & inhibitors*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*


  • CD3 Complex
  • CD3 antigen, gamma chain
  • Isoenzymes
  • RNA, Small Interfering
  • Receptors, Antigen, T-Cell
  • Prkca protein, mouse
  • Prkcq protein, mouse
  • Protein Kinase C
  • Protein Kinase C-alpha
  • Protein Kinase C-theta
  • Leucine