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KIR on the cusp of modern immunogenetics

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Killer Immunoglobulin-like Receptors (KIR) and their Human Leukocyte Antigen (HLA) ligands play a central role in immunity and human health. These molecules are encoded by gene families with copy number variation, extreme levels of sequence diversity and complex expression patterns. The rapid evolution of KIR and HLA genes and their associations with infectious diseases, pregnancy disorders, immunopathologies and outcome of cell transplantation has generated considerable in-terest from immunologists, geneticists and clinicians. Until recently, however, analyses have been stuck at low-level resolution, focussing primarily on presence or absence of KIR genes. This is changing with the advent of modern high throughput sequencing, cell phenotyp-ing, and bioinformatics. These developments allow high-resolution analysis and much deeper un-derstanding of KIR evolution and KIR function. The impending deluge of high dimensional data brings inevitably new challenges in analysis, interpretation and communication of re-sults, but the benefits are already tangible. The diversity of KIR across worldwide human popula-tions is being catalogued at the allele level. Structures of KIR molecules and their interactions with HLA-peptide complexes are being determined. How KIR modulate natural killer (NK) cell education is being defined. Ligands for activating KIR, elusive for many years, are being discovered. KIR gene complexes and their related receptor gene families are being characterised in animal models and livestock breeds. These advances are helping generate a more complete picture of the impact of KIR variation in health and disease and offer new opportunities for immunotherapy, as highlight-ed in a recent meeting*.



Genomics, Killer-cell immunoglobulin-like receptors, MHC/HLA, natural killer cell, Animals, Female, HLA Antigens, Humans, Immunogenetic Phenomena, Infections, Killer Cells, Natural, Male, Pregnancy, Receptors, KIR

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Wellcome Trust (200841/Z/16/Z)
European Research Council (695551)
We are grateful to Graham Burton (Director of the Centre for Trophoblast Research, University of Cambridge), as well as the Wellcome Trust and the British Society for Immunology, for their sup-port, to John Trowsdale for critically reading this report, and to Oisin Huhn and Norman Shreeve for help with the organisation. James Traherne’s research is funded by the European Research Coun-cil under the European Union's Horizon 2020 research and innovation programme (Grant 695551). A Wellcome Trust Investigator Award (Grant 200841/Z/16/Z) and the Centre for Trophoblast Research fund Francesco Colucci’s research.