T-cell recognition in health and disease: The role of self-peptides and high-throughput analysis of the response to a cancer vaccine

摘要: We are interested in the molecular requirements for T-cell activation and subsequent signaling, as well as applying this knowledge to understand and manipulate the human response to cancer. To this end, we have been developing single cell imaging methodologies in order to precisely quantitate the number of agonist peptide ligands that αβ T cells need to "see" in order to initiate and sustain T-cell activation. Remarkably, four out of four T cells can begin activation when in contact with even a single peptide-MHC complex on the surface of another cell. This shows that agonist dimers could not be the "trigger" for activation and thus we have proposed a model (the "pseudodimer hypothesis") in which particular endogenous peptide-MHC complexes ("co-agonists") can synergize with individual agonist ligands to initiate a signaling cascade. We have obtained substantial support for this model with recent …