Structure/function of human killer cell immunoglobulin-like receptors: lessons from polymorphisms, evolution, crystal structures and mutations
- 7 January 2011
- journal article
- review article
- Published by Wiley in Immunology
- Vol. 132 (3), 315-325
- https://doi.org/10.1111/j.1365-2567.2010.03398.x
Abstract
Stimulation or tolerance of natural killer (NK) cells is achieved through a cross-talk of signals derived from cell surface activating and inhibitory receptors. Killer cell immunoglobulin-like receptors (KIR) are a family of highly polymorphic activating and inhibitory receptors that serve as key regulators of human NK cell function. Distinct structural domains in different KIR family members determine function by providing docking sites for ligands or signalling proteins. Here, we review a growing body of literature that has identified important structural elements on KIR that contribute to function through studies of engineered mutants, natural polymorphic sequence variants, crystal structure data and the conservation of protein sequences throughout primate evolution. Extensive natural polymorphism is associated with both human KIR and their ligands, MHC class I (HLA-A, -B and -C) molecules, and numerous studies have demonstrated associations between inheritance of certain combinations of KIR and HLA genes and susceptibility to several diseases, including viral infections, autoimmune disorders and cancers. In addition, certain KIR/HLA combinations can influence pregnancy and the outcome of haematopoietic stem cell transplantation. In view of the significant regulatory influences of KIR on immune function and human health, it is essential to fully understand the impacts of these polymorphic sequence variations on ligand recognition, expression and function of the receptor.Keywords
This publication has 91 references indexed in Scilit:
- IPD—the Immuno Polymorphism DatabaseNucleic Acids Research, 2009
- KIR2DS4 is a product of gene conversion with KIR3DL2 that introduced specificity for HLA-A*11 while diminishing avidity for HLA-CThe Journal of Experimental Medicine, 2009
- HLA Class I Subtype-Dependent Expansion of KIR3DS1 + and KIR3DL1 + NK Cells during Acute Human Immunodeficiency Virus Type 1 InfectionJournal of Virology, 2009
- Meiotic recombination generates rich diversity in NK cell receptor genes, alleles, and haplotypesGenome Research, 2009
- Dramatically reduced surface expression of NK cell receptor KIR2DS3 is attributed to multiple residues throughout the moleculeGenes & Immunity, 2008
- Human natural killer cellsBlood, 2008
- HLA alleles determine differences in human natural killer cell responsiveness and potencyProceedings of the National Academy of Sciences of the United States of America, 2008
- G Protein–Coupled Receptor Sorting to Endosomes and LysosomesAnnual Review of Pharmacology and Toxicology, 2008
- Differential natural killer cell–mediated inhibition of HIV-1 replication based on distinct KIR/HLA subtypesThe Journal of Experimental Medicine, 2007
- Regulation of NMDA receptors by phosphorylationNeuropharmacology, 2007