The Efficiency of Antigen Recognition by CD8+ CTL Clones Is Determined by the Frequency of Serial TCR Engagement
| Autor: | Hudrisier, D., Kessler, B., Salvatore Valitutti, Horvath, C., Cerottini, J. C., Luescher, I. F. |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Cytotoxicity
Immunologic Mice Inbred BALB C Immunology Receptors Antigen T-Cell Epitopes T-Lymphocyte Membrane Proteins hemic and immune systems chemical and pharmacologic phenomena CD8-Positive T-Lymphocytes Cytotoxicity Tests Immunologic Ligands Clone Cells Mice Inbred C57BL Immunoglobulin Fab Fragments Mice Animals Immunology and Allergy Phosphorylation Antibodies Blocking Peptides Signal Transduction |
| Zdroj: | Europe PubMed Central Web of Science ResearcherID |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Using H-2Kd-restricted CTL clones, which are specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite peptide PbCS252–260 (SYIPSAEKI) and permit assessment of TCR-ligand interactions by TCR photoaffinity labeling, we have previously identified several peptide derivative variants for which TCR-ligand binding and the efficiency of Ag recognition deviated by fivefold or more. Here we report that the functional CTL response (cytotoxicity and IFN-γ production) correlated with the rate of TCR-ligand complex dissociation, but not the avidity of TCR-ligand binding. While peptide antagonists exhibited very rapid TCR-ligand complex dissociation, slightly slower dissociation was observed for strong agonists. Conversely and surprisingly, weak agonists typically displayed slower dissociation than the wild-type agonists. Acceleration of TCR-ligand complex dissociation by blocking CD8 participation in TCR-ligand binding increased the efficiency of Ag recognition in cases where dissociation was slow. In addition, permanent TCR engagement by TCR-ligand photocross-linking completely abolished sustained intracellular calcium mobilization, which is required for T cell activation. These results indicate that the functional CTL response depends on the frequency of serial TCR engagement, which, in turn, is determined by the rate of TCR-ligand complex dissociation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|