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A Novel System of Polymorphic and Diverse NK Cell Receptors in Primates

Averdam, A; Petersen, B; Rosner, C; Neff, J; Roos, C; Eberle, M; Aujard, F; ... Walter, L; + view all (2009) A Novel System of Polymorphic and Diverse NK Cell Receptors in Primates. PLOS GENET , 5 (10) , Article e1000688. 10.1371/journal.pgen.1000688. Green open access

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Abstract

There are two main classes of natural killer (NK) cell receptors in mammals, the killer cell immunoglobulin-like receptors (KIR) and the structurally unrelated killer cell lectin-like receptors (KLR). While KIR represent the most diverse group of NK receptors in all primates studied to date, including humans, apes, and Old and New World monkeys, KLR represent the functional equivalent in rodents. Here, we report a first digression from this rule in lemurs, where the KLR (CD94/NKG2) rather than KIR constitute the most diverse group of NK cell receptors. We demonstrate that natural selection contributed to such diversification in lemurs and particularly targeted KLR residues interacting with the peptide presented by MHC class I ligands. We further show that lemurs lack a strict ortholog or functional equivalent of MHC-E, the ligands of nonpolymorphic KLR in "higher" primates. Our data support the existence of a hitherto unknown system of polymorphic and diverse NK cell receptors in primates and of combinatorial diversity as a novel mechanism to increase NK cell receptor repertoire.

Type: Article
Title: A Novel System of Polymorphic and Diverse NK Cell Receptors in Primates
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pgen.1000688
Publisher version: http://dx.doi.org/10.1371/journal.pgen.1000688
Language: English
Additional information: This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. This study was supported by grants from the Deutsche Forschungsgemeinschaft (GRK 289) to JN and LW and by the Nationales Genomforschungsnetz (NGFN) to RR. AA was in part supported by the European Commission (contract 28594). PC, HS, and SB were supported by the Wellcome Trust. The contribution of MC was funded whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. LAR was supported by National Institutes of Health Grant AI 31168 to Peter Parham. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: MAJOR HISTOCOMPATIBILITY COMPLEX, CLASS-I MOLECULES, NATURAL-KILLER-CELLS, HLA-E BINDS, MAXIMUM-LIKELIHOOD, MICROCEBUS-MURINUS, SEQUENCE ALIGNMENT, GENE-COMPLEX, MIXED MODELS, EVOLUTION
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/172149
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