Sustained Interactions between T Cell Receptors and Antigens Promote the Differentiation of CD4+ Memory T Cells

• CD4+ TCR repertoires skew after the emergence of memory T cells
• Memory T cell differentiation corresponds to a loss of TCR repertoire diversity
• MHC class II tetramer off rate, but not avidity, predicts memory T cell potential
• Sustained TCR interactions with antigens promote memory T cell fate decisions

SummaryDuring CD4+ T cell activation, T cell receptor (TCR) signals impact T cell fate, including recruitment, expansion, differentiation, trafficking, and survival. To determine the impact of TCR signals on the fate decision of activated CD4+ T cells to become end-stage effector or long-lived memory T helper 1 (Th1) cells, we devised a deep-sequencing-based approach that allowed us to track the evolution of TCR repertoires after acute infection. The transition of effector Th1 cells into the memory pool was associated with a significant decrease in repertoire diversity, and the major histocompatibility complex (MHC) class II tetramer off rate, but not tetramer avidity, was a key predictive factor in the representation of individual clonal T cell populations at the memory stage. We conclude that stable and sustained interactions with antigens during the development of Th1 responses to acute infection are a determinative factor in promoting the differentiation of Th1 memory cells.