Inhibition of TCR triggering by a spectrum of altered peptide ligands suggests the mechanism for TCR antagonism

Détails

ID Serval
serval:BIB_3275DD7EE408
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Inhibition of TCR triggering by a spectrum of altered peptide ligands suggests the mechanism for TCR antagonism
Périodique
European Journal of Immunology
Auteur(s)
Bachmann  M. F., Speiser  D. E., Zakarian  A., Ohashi  P. S.
ISSN
0014-2980 (Print)
Statut éditorial
Publié
Date de publication
10/1998
Volume
28
Numéro
10
Pages
3110-9
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Oct
Résumé
Understanding the parameters involved in T cell activation has been complicated by the discovery of partial T cell agonists. Altered peptide ligands (APL) have recently shown that different subsets of T cell responses can be selectively activated by certain peptides, which define a hierarchy of T cell activation. For cytotoxic T cells, this hierarchy ranges from sensitizing target cells for lysis through proliferation to effector cell induction. The degree of TCR down-regulation mediated by APL-MHC interactions correlates well with the induction of specific T cell effector functions. This suggests that the potential agonist response induced by a given peptide occurs at different triggering thresholds. To examine the relative agonist and antagonist functions of different peptides, we have investigated the ability of lymphocytic choriomeningitis virus glycoprotein-derived APL to induce or inhibit a range of effector functions in naive CD8+ T cells. By this, we have defined a hierarchy of peptides that display a range of properties from strong agonist to no agonist function. At each level, peptides that were ranked lower in this hierarchy were able to interfere or antagonize the induction of effector functions by higher ranking peptides. We have therefore shown that this spectrum of peptides ranging from strong to no agonist function has an inverse gradient from strong antagonist to no antagonist function. Moreover, the ability of the different peptides to inhibit TCR internalization correlated with their ranking within the hierarchy. These findings support the model that antagonists are effectively preventing TCR oligomerization and functional TCR triggering.
Mots-clé
Animals Antigen Presentation *Antigens, Viral Cell Division Cells, Cultured Down-Regulation Epitopes, T-Lymphocyte/*immunology Glycoproteins/*immunology/pharmacology Ligands Macrophages/drug effects/immunology Mice Mice, Transgenic Peptide Fragments/*immunology/pharmacology Receptors, Antigen, T-Cell/antagonists & inhibitors/genetics/*immunology T-Lymphocytes/*immunology *Viral Proteins
Pubmed
Web of science
Création de la notice
28/01/2008 12:32
Dernière modification de la notice
20/08/2019 14:18
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