Gradual changes within long-lived influenza virus-specific CD8 T cells are associated with the loss of public TCR clonotypes in older adults

Abstract

Background: Susceptibility to life-threatening influenza increases with age, partly due to declining immunity. Frequency, phenotype and T-cell receptor (TCR) composition of influenza-specific CD8+ T-cells directed at the prominent A2/M158 influenza epitope change across the human lifespan. Methods: We investigated longevity and mechanisms underlying age-related changes in influenza-specific TCR repertoires by performing longitudinal analyses in young and older adults across 7–12 years within A2/M158+CD8+ T-cells using peptide-HLA tetramers directly ex vivo. Paired TCRαβ-chains were used to track clonotypes over time within individuals. Findings: Expanded public and private TCR clonotypes wer..