Clonotypic structure of human memory alpha-T cell repertoires to influenza in elderly individuals (45.20)

Abstract

Abstract The age-associated thymic atrophy and reduced repertoires of naïve T cells could be confounding factors of high morbidity and mortality of older populations due to the seasonal influenza infections. Given that influenza A viral epitope M158-66 induces robust CD8 T cell responses among middle-aged populations, we examined clonotypical α-TCR repertoires among older blood donors. Previously we reported that α-TCR repertoires in middle-age individuals are polyclonal where M158-66 specific T cells were selected as memory cells due to expression JA42 α -chains with poly-G/S/A runs in the CDR3. In the present study we compare α-TCR repertoires between middle-aged and older individuals in respect to Vα family usage and clonotypical diversities. Using CDR3α- spectratyping and sequencing, we found that middle-aged adults possess stable polyclonal response to influenza where diverse JA42 CD8 T cells are distributed among eleven Vα families and VA27 family was dominated in vitro response. In contrary, with aging such dominance was still present in some but not all individuals. Two subjects responses to M158-66 was mediated by VA12.1 family, which represents minor component in the middle-aged cohort. In addition to reduced diversity of VA families, the older subjects posses reduced diversity of JA42 clonotypes. Therefore, we concluded that influenza re-exposure during lifetime induces clonotypical exhaustion of T cells leading to reshaping of T cell repertoire.