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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.

Original publication

DOI

10.1002/eji.1830270912

Type

Journal article

Journal

Eur J Immunol

Publication Date

09/1997

Volume

27

Pages

2195 - 2203

Keywords

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