QUANTITATIVE-ANALYSIS OF T-CELL ACTIVATION - ROLE OF TCR LIGAND DENSITY AND TCR AFFINITY

(B6xA)F-1 mice were immunized with sperm whale myoglobin, and T cell c lones and hybridomas were generated. Hybridoma 74a.e9 was specific for the sperm whale myoglobin 67-79 peptide and could be partially activa ted by a peptide analogue, equine myoglobin with a natural 74G substit ution. Using this hybridoma in T cell activation assays, we studied th e effects of varying the avidity of the TCR for its ligand, the concen tration of MHC:peptide complex on the APC, and the density of TCR on t he surface. Varying ligand concentration on the surface of the APC, th e TCR avidity, or the density of TCR on the T cell were equally import ant parameters in driving T cell activation. The mouse myoglobin (74T) analogue, however, acted as an antagonist to the T cell response. Its effectiveness was also partially determined by its ability to bind to MHC. By independently altering each of these variables and following T cell activation, we describe the interrelationships among these thre e components (MHC:peptide:TCR) that control the activation of the T ce ll.