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

Abstract

SummaryKiller-cell 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 have generated considerable interest from immunologists, geneticists and clinicians. Until recently, however, analyses have been stuck at low-level resolution, focusing primarily on presence or absence of KIR genes. This is changing with the advent of modern high throughput sequencing, cell phenotyping and bioinformatics. These developments allow high-resolution analysis and much deeper understanding of KIR evolution and KIR function. The impending deluge of high dimensional data brings inevitably new challenges in analysis, interpretation and communication of results, but the benefits are already tangible. The diversity of KIR across worldwide human populations 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 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 characterized in animal models and livestock breeds. These advances are helping to generate a more complete picture of the impact of KIR variation in health and disease and offer new opportunities for immunotherapy, as highlighted in a recent meeting (The Tenth KIR Workshop, April 2017 Cambridge, UK).

Decidual Vasculopathy in Preeclampsia and Spiral Artery Remodeling Revisited: Shallow Invasion versus Failure of Involution

“… 27 28 The complex interaction of KIR and HLA-C in addition to complex KIR gene structures and expressions on NK cells may lead to preeclampsia and other pregnancy-related complications such as intrauterine growth restriction, recurrent miscarriage, and diabetes. 29 30 31 There are many recent reviews on this topic; our interest in KIR system is centered on decidual vasculopathy in preeclampsia and others pregnancy-related complications, 25 32 and decidual vasculopathy appears to result from the combination of the endovascular fetal trophoblasts and CD56 expression provided by the maternal uterine NK cells. It is plausible that persistence of the endovascular trophoblasts in decidual vasculopathy results from the specific interaction of KIR and HLA-C, leading to fetal trophoblasts, rather than uterine NK cells, to survive longer.…”

Natural killer cell transcriptional control, subsets, receptors and effector function

“…3,4 Colucci and Traherne summarized the impacts of high-dimensional data from high-throughput sequencing for enhanced understanding of killer cell immunoglobulin-like receptor (KIR) evolution and function, including effects on NK cell education. 3 Along with these breakthroughs has come the added dimension of the knowledge that KIR binding to HLA I alleles can be exquisitely sensitive to modulation by bound peptide. 5 There are ramifications of this model both with respect to modulation of NK cell KIR regulation by alterations in the self-peptide repertoire and by peptides derived from viral infection.…”

“…2 Furthermore, with the improved ability to define the complexity of NK cell ligand recognition, inhibition, activation, subsets and effector function has come the realization that these cells offer a rewarding seam for exploration and therapeutic manipulation.Two recent papers have offered rather comprehensive updates on the constantly emerging understanding of the synthesis of NK cell inhibitory and activating receptor recognition. 3,4 Colucci and Traherne summarized the impacts of high-dimensional data from high-throughput sequencing for enhanced understanding of killer cell immunoglobulin-like receptor (KIR) evolution and function, including effects on NK cell education. 3 Along with these breakthroughs has come the added dimension of the knowledge that KIR binding to HLA I alleles can be exquisitely sensitive to modulation by bound peptide.…”

Bioinformatics for immunologists

“…Rachael Bashford Rogers recently guest edited a thematic review series on new approaches to high‐throughput immune receptor sequencing and its analysis. Within immune receptor curation, we now consider not just B‐cell receptors (BCR) and TCR, but also approaches to natural killer cell receptor sequencing to understand the functionality of the killer immunoglobulin‐like receptors repertoire …”