Peptide-induced T cell receptor down-regulation on naive T cells predicts agonist/partial agonist properties and strictly correlates with T cell activation

Eur J Immunol. 1997 Sep;27(9):2195-203. doi: 10.1002/eji.1830270912.


Recent experiments defining T cell agonists, partial agonists and antagonists have suggested that the T cell can discriminate between subtle differences in interactions leading to T cell activation. To further understand the complexities of T cell activation, we have analyzed the requirements for the induction of a variety of effector functions using naive T cells and a variety of altered peptide ligands. Using a strong agonist peptide, massive T cell receptor (TCR) down-regulation correlated with a wide range of effector functions that were all induced above the same threshold peptide concentration. Interestingly, the kinetics of TCR down-regulation correlated with the concentration of the peptide, whereas the maximal degree of TCR down-regulation correlated with the induction of all monitored effector functions. A selected group of altered peptide ligands was also examined that were able to render target cells susceptible for lysis by effector cytotoxic T lymphocytes. The extent of TCR down-regulation induced by these peptides corresponded to the induction of a subset of effector functions. These studies have shown that the extent of TCR down-regulation defines the strength of TCR-mediated "signal 1" which correlates with the spectrum of effector functions activated within the T cell. Thus, activation of different T cell functions requires the triggering of distinct numbers of TCR. The different parameters that influence TCR down-regulation define important distinctions between our results and previously reported findings with T cell clones and may outline decisive parameters for the consequences of T cell activation in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Viral / immunology
  • Cytotoxicity, Immunologic
  • Dose-Response Relationship, Immunologic
  • Down-Regulation
  • Endocytosis
  • Lymphocyte Activation
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Peptides / immunology
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • T-Lymphocytes / metabolism*
  • Thymus Gland / cytology


  • Antigens, Viral
  • Peptides
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta