Agonist-induced T Cell Receptor Down-Regulation: Molecular Requirements and Dissociation From T Cell Activation

Eur J Immunol. 1997 Jul;27(7):1769-73. doi: 10.1002/eji.1830270726.

Abstract

T cell receptor (TCR) down-regulation is a consequence of specific receptor engagement and plays an important role in modulating the T cell response. We have investigated the role of protein kinase C (PKC) and protein tyrosine kinases (PTK) in the induction of TCR down-regulation. We report that the mutation of S126 in the CD3-gamma chain that is known to inhibit phorbol-12-myristate 13-acetate-induced TCR down-regulation does not affect down-regulation induced by a specific agonist. In addition, agonist-induced TCR down-regulation is not affected by blockade or depletion of PKC, neither by blockade or lack of PTK, while the same treatments efficiently interfere with T cell activation. These results demonstrate that TCR down-regulation is induced by early events which follow specific engagement by an agonist and can be dissociated from those required for full T cell activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD3 Complex / physiology
  • Down-Regulation / drug effects
  • Down-Regulation / immunology*
  • Enzyme Activation / drug effects
  • Enzyme Activation / immunology
  • Humans
  • Jurkat Cells
  • Lymphocyte Activation / drug effects*
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Receptors, Antigen, T-Cell / agonists
  • Receptors, Antigen, T-Cell / drug effects*
  • Receptors, Antigen, T-Cell / metabolism*
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology
  • src-Family Kinases / physiology

Substances

  • CD3 Complex
  • Receptors, Antigen, T-Cell
  • Protein-Tyrosine Kinases
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • src-Family Kinases
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate