Extending killer Ig-like receptor function: from HLA class I recognition to sensors of microbial products

Abstract

Killer Ig-like receptors (KIRs) are human natural killer (NK) receptors that recognize allotypic determinants of human leukocyte antigen (HLA) class I. Inhibitory KIRs discriminate normal cells from tumour or virus-infected cells that have lost or reduced HLA class I expression. Donor NK cell "alloeffector" responses are exploited in haploidentical haematopoietic stem cell transplantation to treat leukaemia. NK cells also express several toll-like receptors (TLRs) that increase NK cell cytotoxicity and cytokine release in response to ligands. Surprisingly, KIR3DL2 binds the TLR ligand CpG-oligodexynucleotides, and together, they are co-internalized and translocated to TLR9-rich early endosomes. This novel KIR-associated function offers clues to understanding the NK cell response to microbial infection, and extends the role played by KIRs in immune defence.