How the strength of peptide-MHC and TCR interaction impacts CD8 T cell responses (132.24)

Abstract

Abstract The pool of naïve T cells specific for any foreign peptide/MHC-I epitope is diverse and contains cells that differ in their functional avidity. Theoretical considerations imply that there are likely to be more low than high avidity T cells specific for any foreign antigen. We studied to what extent lower avidity T cells participate in an immune response and we investigated how the dominance of high avidity T cells evolves over the course of an infection. To control the strength of stimulation that CD8 T cells receive during an immune response, we used a model system in which OT-1 TCR transgenic CD8 T cells were stimulated during a Listeria monocytogenes infection either by their native ligand SIINFEKL or by different SIINFEKL-derived altered peptide ligands. Using this system we observed that even very weak TCR-ligand interactions are sufficient to induce rapid T cell proliferation and to generate functional effector and memory CD8 T cells. However, the strength of the TCR-ligand interaction impacts when expansion stops and contraction begins and when the cells exit lymphoid organs, i.e. strongly stimulated T cells contract and exit lymphoid organs later than do weakly stimulated cells. Our data challenges the prevailing view that strong TCR ligation is a prerequisite for CD8+ T cell activation. Instead, very weak interactions are sufficient for activation, but strong TCR ligation is required to sustain T cell expansion.