Different Evolution of Inhibitory and Activating Killer Immunoglobulin Receptors (KIR) in Worldwide Human Populations

Derek Middletona, b, Ashley Meenagha, Juan Ignacio Serrano-Velac, Juan Moscosoc, Antonio Arnaiz-Villena*, c
a Northern Ireland Histocompatibility and Immunogenetics Laboratory, City Hospital, Belfast, Northern Ireland
b School of Biological Sciences, University of Ulster, Coleraine, Northern Ireland
c Department of Immunology, University Complutense, The Madrid Regional Blood Center, Madrid, Spain

© 2008 Middleton et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Departamento de Immunologia, Facultad de Medicina, Universidad Complutense de Madrid, Avenida Complutense s/n, 28040, Madrid, Spain; Tel: +34 91 301 7356; Fax: +34 91 301 7354;


HLA class I molecules are ligands for natural killer cells’ inhibitory (KIR DL) and activating (KIR DS) receptors. KIR DL receptors have a greater avidity for HLA class I molecules than KIR DS receptors. Thus, there is a possibility that HLA molecules drive KIR receptor selection.

We have used the percentage of individuals bearing the genes KIR 3DS1, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 2DL1, 2DL2, 2DL3, 2DL5 and 3DL1 in relatively well defined populations to test whether there is a different way of relating worldwide populations between KIR DS and KIR DL molecules.

We have used ARLEQUIN, DISPAN and VISTA computer programs to construct dendrograms and correspondence analyses showing the genetic relationships among different human world populations. Analyses based on KIR DS or KIR haplotype B genes show that populations are related according to geography, like a good anthropological marker (i.e.: HLA or Y chromosome systems). The results based on KIR DL or KIR haplotype A genes do not show such a correlation. Results are discussed taking into account the linkage of both HLA and KIR systems to microbial diseases and the possible evolutionary shaping of both HLA and KIR receptors repertoire by pathogens.

Keywords: Activating KIR, HLA, inhibitory KIR, populations.