1B-O1-1625 PDF
Defining NK cell repertoire diversity by mass cytometry
Natural killer (NK) cells are essential for immune defense and reproduction, yet remain poorly understood as one of the major lymphocyte populations. NK cell activation is controlled by the integration of activating and inhibitory signals. NK cell diversity and function are closely linked. Using mass cytometry, we provide an unprecedented understanding of NK cell repertoire diversity. We simultaneously analyzed 37 parameters, including 28 NK cell receptors, on peripheral blood NK cells from 5 sets of monozygotic twins and 12 unrelated donors of defined human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptor (KIR) genotype. This analysis revealed a remarkable degree of NK cell diversity, with an estimated 6000 to 30,000 phenotypic populations within an individual and >100,000 phenotypes in the donor panel. Genetics largely determines inhibitory receptor expression, whereas activation receptor expression is heavily influenced by environmentally factors. Thus, NK cells may maintain self-tolerance through strictly regulated expression of inhibitory receptors while using adaptable expression patterns of activating and costimulatory receptors to rapidly respond to pathogens and tumors. These findings emphasize the possibility that discrete NK cell subpopulations can be harnessed for immunotherapeutic strategies in the settings of infection, reproduction, and transplantation.