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

Details

Serval ID
serval:BIB_4A256FBEA846
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Peptide-induced T cell receptor down-regulation on naive T cells predicts agonist/partial agonist properties and strictly correlates with T cell activation
Journal
European Journal of Immunology
Author(s)
Bachmann  M. F., Oxenius  A., Speiser  D. E., Mariathasan  S., Hengartner  H., Zinkernagel  R. M., Ohashi  P. S.
ISSN
0014-2980 (Print)
Publication state
Published
Issued date
09/1997
Volume
27
Number
9
Pages
2195-203
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Sep
Abstract
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.
Keywords
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
Pubmed
Web of science
Create date
28/01/2008 11:33
Last modification date
20/08/2019 13:57
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