title: Peptide-induced T cell receptor down-regulation on naive T cells predicts agonist/partial agonist properties and strictly correlates with T cell activation.
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.
authors.affiliation: Ontario Cancer Institute, Department of Medical Biophysics, Toronto, Canada. bachmann@oci.utoronto.ca
authors.forename: M F
authors.initials: MF
authors.lastname: Bachmann
authors.forename: A
authors.initials: A
authors.lastname: Oxenius
authors.forename: D E
authors.initials: DE
authors.lastname: Speiser
authors.forename: S
authors.initials: S
authors.lastname: Mariathasan
authors.forename: H
authors.initials: H
authors.lastname: Hengartner
authors.forename: R M
authors.initials: RM
authors.lastname: Zinkernagel
authors.forename: P S
authors.initials: PS
authors.lastname: Ohashi
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation; D004705:Endocytosis; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology
chemical_list: D000956:Antigens, Viral; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta