Regulation of memory CD4 T cell repertoire diversity upon peptide and protein vaccination (160.18)

Diverse antigen-specific memory TCR repertoires are essential for protection against pathogens. Subunit vaccines that combine peptide or protein antigen with TLR agonists are very potent in inducing T cell immune responses but their capacity to elicit stable and diverse memory CD4 T cell repertoire has not been evaluated. Here, we tracked the development of antigen-specific memory CD4 T cells after peptide or protein vaccination. Both vaccination regimens induced equally diverse effector CD4 TCR repertoires but a skewing toward high affinity clonotypes was observed in the memory TCR repertoire elicited by peptide vaccines. This skewing did not occur after protein vaccination leaving the antigen-specific TCR repertoire essentially intact in the transition from effector to memory. Clear understanding of the factors regulating the TCR repertoire diversity after peptide and protein vaccination contributes to our knowledge of T-cell mediated immune responses and has practical relevance to the design of vaccines against infections requiring robust T cell immunity.