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Cambridge Immunology Network



The KIR complex appears to be evolving rapidly in humans, and more than 50 different haplotypes have been described, ranging from four to 14 KIR loci. All KIR loci are subject to copy number variation (CNV). The evolutionary plasticity of the KIRs and their broad biomedical relevance makes it important to understand how these immune receptors evolve.  Intense selection pressure by pathogens presumably accounts for the marked variability and leads to susceptibility to autoimmunity for some alleles. The heightened propensity to generate novel hybrid KIR receptors may provide a proactive evolutionary measure, to militate against pathogen evasion or subversion. We propose that CNV in KIR is an evolutionary strategy, which KIR typing for disease association must take into account.


Key publications: 

Nakimuli A, Chazara O, Farrell L, Hiby SE, Tukwasibwe S, Knee O, Jayaraman J, Traherne JA, Elliott AM, Kaleebu P, Mirembe F, Moffett A. Killer cell immunoglobulin-like receptor (KIR) genes and their HLA-C ligands in a Ugandan population. Immunogenetics. 2013 Nov;65(11):765-75.

Béziat V, Traherne JA, Liu LL, Jayaraman J, Enqvist M, Larsson S, Trowsdale J, Malmberg KJ. Influence of KIR gene copy number on natural killer cell education. Blood. 2013 Jun 6;121(23):4703-7.

Jiang W, Johnson C, Jayaraman J, Simecek N, Noble J, Moffatt MF, Cookson WO, Trowsdale J, Traherne JA. Copy number variation leads to considerable diversity for B but not A haplotypes of the human KIR genes encoding NK cell receptors. Genome Res. 2012 Oct;22(10):1845-54.

Hov JR, Kosmoliaptsis V, Traherne JA, Olsson M, Boberg KM, Bergquist A, Schrumpf E, Bradley JA, Taylor CJ, Lie BA, Trowsdale J, Karlsen TH. Electrostatic modifications of the human leukocyte antigen-DR P9 peptide-binding pocket and susceptibility to primary sclerosing cholangitis. Hepatology. 2011 Jun;53(6):1967-76.

Espeli M, Niederer HA, Traherne JA, Trowsdale J, Smith KG. Genetic variation, Fcγ receptors, KIRs and infection: the evolution of autoimmunity. Curr Opin Immunol. 2010 Dec;22(6):715-22.

Traherne JA, Martin M, Ward R, Ohashi M, Pellett F, Gladman D, Middleton D, Carrington M, Trowsdale J. Mechanisms of copy number variation and hybrid gene formation in the KIR immune gene complex. Hum Mol Genet. 2010 Mar 1;19(5):737-51.


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