Trogocytosis efficiency and trogocytosis-mediated signaling correlates with TCR affinity for MHC: peptide ligands 2579

Abstract Description At the immunological synapse, T cells capture antigen presenting cell (APC) membrane associated membrane proteins in a process termed trogocytosis. We have previously shown that APC-derived molecules, such as cognate MHC:peptide, engage cognate receptors on CD4+ T cells driving intracellular signaling. This leads to activation, effector subset differentiation and selective survival of trogocytosis positive (trog+) cells. While the role of antigen affinity on T cell activation and T cell Receptor (TCR) signaling has been well studied, the impact on trogocytosis efficiency and subsequent trogocytosis-mediated signaling remains unknown. To address this question, primary 5C.C7 T cells were co-cultured with APCs pulsed with moth cytochrome C (MCC88-103) or the altered peptide ligands K5 (heteroclitic peptide), T102S (a weak agonist), or K99A (a very weak agonist). We found that for naïve T cells, the efficiency of trogocytosis is dependent upon TCR affinity for the peptide. Four days after removal from APCs, trog+ T cells displayed an activated phenotype, but had not proliferated. Somewhat unexpectedly, trogocytosis by in vitro activated T cell blasts is much less sensitive to peptide affinity compared to naïve T cells. Experiments are underway to define the mechanism behind these differences. Funding Sources NIAID R15AI147034 Topic Categories Antigen and Dendritic Cell Processing, Presentation, and Biology (AGDC)