Maintenance of memory CD8+ T cell diversity and proliferative potential by a primary response upon re-challenge

Memory CD8+ T cells generated during an immune response are long lived and self-renewing, offering enhanced host protection against re-infection. However, how an antigen-specific population of memory T cells is maintained, throughout repetitive infections over potentially a lifetime, is not known. Here we show that a primary response during re-challenge significantly contributes to memory T cell pool both qualitatively and quantitatively. Upon re-challenge, the skewed Vbeta usage and TCR repertoire of pre-existing memory T cells is partly corrected by diversity in a newly primed (primary) T cell population. Importantly, this primary population expands more vigorously in a subsequent antigen encounter. These findings indicate that memory T cell populations evolve over multiple challenges, favoring memory T cells generated in more recent encounters, and suggest that these primary populations have essential roles in the perpetuation of antigen-specific T cell populations.