The neutrophil recombinatorial TCR-like immune receptor is expressed across the entire human life span but repertoire diversity declines in old age.

Abstract Recent evidence has revealed the existence of T cell receptor (TCR) αβ-based recombinatorial immune receptors in phagocytes. Here, we performed a systematic survey of the variable β-chain repertoires of the neutrophil TCR-like αβ immunoreceptor (referred to as TCRL n αβ) in defined cohorts of young and old individuals. Peripheral blood CD15 + neutrophils from young adults (age 30 ± 7 years, n  = 12) expressed an average number of 13 ± 6 distinct TCRL n Vβ-chains from the total pool of 25 human Vβ-chains. Neutrophils from aged subjects (age 76 ± 6 years, n  = 12) also consitutively express the TCRL n , however, only a small number of Vβ-chains is used (4 ± 2). Consistent with this, the average number of expressed CDR3 Vβ length variants was fourfold higher in young individuals than in aged subjects (33 ± 24 vs. 8 ± 3). Young adults showed broad usage of all TCRL n Vβ-chains. In contrast, >70 years individuals displayed a striking repertoire polarization towards the TCRL n Vβ1 and Vβ5b chains and a high degree of Vβ5b clonotype sharing. Our study reveals broad TCRL n repertoire diversity in young adults and demonstrates that the neutrophil variable immune receptor is expressed throughout the entire human life span. The marked decline in TCRL n repertoire diversity in old age identifies a novel mechanism of immunosenescence in neutrophils.