The efficiency of antigen recognition by CD8+ CTL clones is determined by the frequency of serial TCR engagement.

Journal article

Using H-2Kd-restricted CTL clones, which are specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite peptide PbCS(252-260) (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-gamma 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.

Authors: Hudrisier, D; Kessler, B; Valitutti, S; Horvath, C; Cerottini, J

• Publication status: Published
• Journal: Journal of Immunology
• Volume: 161
• Issue: 2
• Pages: 553-562
• Publication date: 1998-07-01
• EISSN: 1550-6606
• ISSN: 0022-1767
• Language: English
• Keywords: Peptides; Epitopes, T-Lymphocyte; Cytotoxicity, Immunologic; CD8-Positive T-Lymphocytes; Antibodies, Blocking; Immunoglobulin Fab Fragments; Mice, Inbred BALB C; Signal Transduction; Phosphorylation; Cytotoxicity Tests, Immunologic; Receptors, Antigen, T-Cell; Membrane Proteins; Mice, Inbred C57BL; Clone Cells; Mice; Ligands; Animals