Discovering the determinants of diversity in the human NK cell repertoire by mass cytometry (P3018)

• DOI: 10.4049/jimmunol.190.supp.114.10
• Publication Date: 2023-01-01T09:12:30Z
• Authors: Amir Horowitz; Dara Strauss-Albee; Neda Nemat-Gorgani; Ozge Dogan; Cornelia Dekker; Sally Mackey; Gary Swan; Mark Davis; Paul Norman; Lisbeth Guethlein; Peter Parham; Catherine Blish
• Keywords: Mass cytometry

Abstract NK cells respond to infected and transformed using germline-encoded receptors (NKRs). Collectively, these NKRs combine form distinct repertoires that tune the cell response. To provide a framework for understanding how perturbations in expression of influence disease pathogenesis, we defined phenotypic heterogeneity 22 healthy individuals (ages 21-62; M=10, F=12), including 5 sets monozygotic twins. Using mass cytometry, surface 38 markers specific lineage identify B cells, T myeloid were examined. KIR HLA class I genotypes determined by Luminex, gene content was further assessed pyrosequencing. populations, as inhibitory NKRs, highly concordant between twins (R2 = 0.90) comparison unrelated 0.66), indicating repertoire is genetically determined. However, when analyzing all twenty-five activating receptors, concordance (R2=0.34) (R2=0.11) greatly decreased, significant environmental determining overall repertoire. Overall, analyses reveal tremendous diversity within both environmentally determined, offer ability examine functional capacity with far greater resolution.