Recent evidence has revealed the existence of T cell receptor (TCR) alpha beta-based recombinatorial immune receptors in phagocytes. Here, we performed a systematic survey of the variable beta-chain repertoires of the neutrophil TCR-like alpha beta immunoreceptor (referred to as TCRLn alpha beta) 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 TCRLn V beta-chains from the total pool of 25 human V beta-chains. Neutrophils from aged subjects (age 76 +/- 6 years, n = 12) also consitutively express the TCRLn, however, only a small number of V beta-chains is used (4 +/- 2). Consistent with this, the average number of expressed CDR3 V beta length variants was fourfold higher in young individuals than in aged subjects (33 +/- 24 vs. 8 +/- 3). Young adults showed broad usage of all TCRLn V beta-chains. In contrast, >70 years individuals displayed a striking repertoire polarization towards the TCRLn V beta 1 and V beta 5b chains and a high degree of V beta 5b clonotype sharing. Our study reveals broad TCRLn 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 TCRLn repertoire diversity in old age identifies a novel mechanism of immunosenescence in neutrophils. (C) 2012 Elsevier Inc. All rights reserved.