The Impact of T Cell Receptor Affinity on Trogocytosis Efficiency and Trogocytosis-Mediated Immune Signaling

Our immune system protects us by identifying and responding to harmful invaders like viruses and bacteria. CD4+ T cells are key players in the mechanisms that are involved in clearance of pathogens (and cancer cells). These T cells respond to infected cells displaying protein fragments (antigens) of the virus or bacteria on their surface. The T cells scan these antigens on the antigen-presenting cells (APC) surface and become activated when they recognize the antigen for which their receptor is specific. During the T cell – APC interaction, membrane and associated membrane proteins are transferred from the APC to the T cell in a process termed trogocytosis. Previous work from our lab has shown that these transferred proteins continue to interact with receptors on the T cells, driving intracellular signaling and participating in the activation and differentiation of the CD4+ T cells. One unresolved question regarding trogocytosis is whether the strength of the interaction between the T cell antigen receptor (TCR) and the antigen (called affinity) impacts the efficiency and subsequent signaling driven by these transferred molecules. T cells recognize protein fragments of these antigens called peptides, one of which is the moth Cytochrome C (MCC). To address this question, primary T cells were co-cultured with APCs pulsed with MCC or altered peptide ligands, including K5 (a strong agonist), T102S (a weak agonist), and K99A (a very weak agonist). We found that for naïve (inactive) T cells, the efficiency of trogocytosis is dependent upon TCR affinity for the peptide. Interestingly, trogocytosis by activated T cells demonstrated reduced sensitivity to peptide affinity compared to naïve T cells. Ongoing experiments aim to understand why these differences exist, which could help improve our knowledge of how the immune system works.