Quantifiable blood TCR repertoire components associate with immune aging

T cell senescence alters the homeostasis of distinct T cell populations and results in decayed adaptive immune protection in older individuals, but a link between aging and dynamic T cell clone changes has not been made. Here, using a newly developed computational framework, Repertoire Functional Units (RFU), we investigate over 6500 publicly available TCR repertoire sequencing samples from multiple human cohorts and identify age-associated RFUs consistently across different cohorts. Quantification of RFU reduction with aging reveals accelerated loss under immunosuppressive conditions. Systematic analysis of age-associated RFUs in clinical samples manifests a potential link between these RFUs and improved clinical outcomes, such as lower ICU admission and reduced risk of complications, during acute viral infections. Finally, patients receiving bone marrow transplantation show a secondary expansion of the age-associated clones upon stem cell transfer from younger donors. Together, our results suggest the existence of a ‘TCR clock’ that could reflect the immune functions in aging populations. Immune aging is associated with altered homeostasis of distinct T cell populations, but a link to clonal dynamic is still not made. Here the authors develop a new framework, Repertoire Functional Units (RFU), and use public TCR sequences to find specific TCR clonal changes that correlate with aged immune repertoires or outcomes of acute viral infection.