Abstract
CD8 T cells play an essential role in controlling viral as well as intracellular bacterial and parasitic infections. Memory CD8 T cells provide protective immunity upon re-encounter with the same pathogens. A better understanding of memory CD8 T cell development is critical for the rational design of vaccines. Transcriptome analyses in antigen-specific CD8 T cells have made a significant contribution to characterize global re-programming of gene expression during memory CD8 T cell differentiation. However, there has been minimal emphasis on understanding translational control of gene expression in antigen specific CD8 T cells. To examine mRNA translation during memory CD8 T cell differentiation, we performed longitudinal analyses of polysome profiles in antigen-specific CD8 T cells after acute LCMV infection. We found that mRNA translation was dynamically regulated during CD8 T cell responses; translation activity was significantly enhanced during clonal expansion phase, and it immediately returned to basal level at the peak of CD8 T cell responses. Genome-wide analyses of mRNA translation showed that a significant number of mRNAs were translationally regulated during CD8 T cell responses. Further experiments revealed that translational control of gene expression plays an important role in memory CD8 T cell formation. Thus, our studies provide a framework for understanding translational regulation that occurs during memory T cell differentiation.