Deciphering the killer‐cell immunoglobulin‐like receptor system at super‐resolution for natural killer and T‐cell biology

Abstract

SummaryKiller‐cell immunoglobulin‐like receptors (KIRs) are components of two fundamental biological systems essential for human health and survival. First, they contribute to host immune responses, both innate and adaptive, through their expression by natural killer cells and T cells. Second, KIR play a key role in regulating placentation, and hence reproductive success. Analogous to the diversity of their human leucocyte antigen class I ligands, KIR are extremely polymorphic. In this review, we describe recent developments, fuelled by methodological advances, that are helping to decipher the KIR system in terms of haplotypes, polymorphisms, expression patterns and their ligand interactions. These developments are delivering deeper insight into the relevance of KIR in immune system function, evolution and disease.

Killer‐cell immunoglobulin‐like receptors on the cusp of modern immunogenetics

“…Second only to HLA genes, killer‐cell immunoglobulin‐like receptor (KIR) genes are the most variable genes in our genome. Expressed in a variegated fashion on subpopulations of natural killer (NK) and T cells, and encoded by genes in the leucocyte receptor complex (LRC) on chromosome 19, KIR form repertoires that vary from individual to individual . Compounding the diversity, HLA class I molecules and KIR interact to regulate the biology of NK cells and T cells.…”

Canonical and cross-reactive binding of NK cell inhibitory receptors to HLA-C allotypes is dictated by peptides bound to HLA-C

“…As there is a very large number of KIR combinations with HLA-C allotypes due to extensive polymorphism of KIR [29,[40][41][42] and of HLA-C, canonical and cross-reactive binding of KIR to HLA-C, and the contribution of peptide to binding, may vary among different KIR-HLA-C combinations. KIR2DL2 and KIR2DL3 cross-reactive binding with C2 indeed varies among C2 allotypes [27].…”

Uterine Natural Killer Cells: Functional Distinctions and Influence on Pregnancy in Humans and Mice

“…KIRs are highly polymorphic receptors encoded within the leukocyte receptor complex (LRC) on chromosome 19, which bind to HLA class I molecules (115). Sixteen KIR genes have been identified and, for each, between 18 and 112 alleles are currently known (116, 117).…”