An archaic HLA class I receptor allele diversifies natural killer cell-driven immunity in First Nations peoples of Oceania.

ABSTRACT: Genetic variation in host immunity impacts the disproportionate burden of infectious diseases that can be experienced by First Nations peoples. Polymorphic human leukocyte antigen (HLA) class I and killer cell immunoglobulin-like receptors (KIRs) are key regulators of natural killer (NK) cells, which mediate early infection control. How this variation impacts their responses across populations is unclear. We show that HLA-A^∗24:02 became the dominant ligand for inhibitory KIR3DL1 in First Nations peoples across Oceania, through positive natural selection. We identify KIR3DL1^∗114, widespread across and unique to Oceania, as an allele lineage derived from archaic humans. KIR3DL1^∗114⁺NK cells from First Nations Australian donors are inhibited through

SUBMITTER: Loh L 

PROVIDER: S-EPMC11606752 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature