Bond lifetime predicts CD4 T cell effector and memory potential 3626

Abstract Description Recognition of antigen and TCR signal strength is a critical step required for T cell survival, expansion, development of effector function and transition towards memory. To better understand T cell kinetic parameters impacting effector and memory bias, we utilized a panel of cloned TCRs specific for the immunodominant CD4 GP61-80 epitope of lymphocytic choriomeningitis virus (LCMV) that we previously show to favor either effector or memory fates. We analyzed the 2D affinity of 4 effector (effector-biased) and 4 memory (memory-biased) clones. All were tetramer positive and of high affinity; However, at the clonal level, affinity did not correlate with the effector or memory outcomes. Recent data on T cell responses to antigen have demonstrated the importance of bond lifetime between TCRs and antigen as they occur under applied cellular forces. After single molecule analysis between TCR and gp66:MHC antigen for 3 effector and 3 memory biased clones, effector fated cells demonstrated significantly longer bond lifetimes than memory fated clones. These data correlate with surrogate markers of TCR signal strength such as ZAP70 phosphorylation and CD25 expression. Our data identify bond lifetime between TCR and antigen as the dominant determining factor of CD4 cell effector versus memory fate during infection. Funding Sources Supported by NIH 5R01AI172253-02 Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)