Newborn and child-like molecular signatures in older adults stem from TCR shifts across human lifespan.

ABSTRACT: CD8⁺ T cells provide robust antiviral immunity, but how epitope-specific T cells evolve across the human lifespan is unclear. Here we defined CD8⁺ T cell immunity directed at the prominent influenza epitope HLA-A*02:01-M1_58-66 (A2/M1₅₈) across four age groups at phenotypic, transcriptomic, clonal and functional levels. We identify a linear differentiation trajectory from newborns to children then adults, followed by divergence and a clonal reset in older adults. Gene profiles in older adults closely resemble those of newborns and children, despite being clonally distinct. Only child-derived and adult-derived A2/M1₅₈⁺CD8⁺ T cells had the potential to differentiate into highly cytotoxic epitope-specific CD8⁺

SUBMITTER: van de Sandt CE 

PROVIDER: S-EPMC10602853 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature