Meeting Report
16
th
IHIW: Population Global Distribution of Killer Immunoglobulin-like
Receptor (KIR) and Ligands
J. A. Hollenbach*, D. G. Augusto†, C. Alaez‡, L. Bubnova§, I. Fae¶, G. Fischer¶,
F. F. Gonzalez-Galarza∥, C. Gorodezky‡, L. Karabon**, P. Kusnierczyk**, J. Noble*,
O. Rickards††, C. Roberts‡‡, M. Schaffer§§, L. Shi¶¶, S. Tavoularis∥∥, E. Trachtenberg*,
Y. Yao¶¶ & D. Middleton***,†††
Summary
In the last fifteen years, published reports have described
KIR gene-content frequency distributions in more than
120 populations worldwide. However, there have been
limited studies examining these data in aggregate to
detect overall patterns of variation at regional and
global levels. Here, we present a summary of the collec-
tion of KIR gene-content data for 105 worldwide
populations collected as part of the 15th and 16th Inter-
national Histocompatibility and Immunogenetics Work-
shops, and preliminary results for data analysis.
Introduction
The killer cell immunoglobulin-like receptors (KIR)
are receptors expressed on natural killer (NK) cells
that function to inhibit or activate NK cells. Several of
the inhibitory KIR use the human leucocyte antigen
(HLA) class I molecules as their ligand, while the
ligands for most of the stimulatory KIR have not been
identified definitively (Biron, 1997; Vales-Gomez et al.,
1998; Vilches & Parham, 2002; Young & Uhrberg,
2002; Hsu, 2004; Smyth et al., 2005; Bashirova et al.,
2006). The KIR gene complex is located on human
chromosome 19q13.4 and is both polygenic and extre-
mely polymorphic. While extensive allelic variability
has been identified, particularly in the inhibitory genes
(http://www.ebi.ac.uk/cgi-bin/ipd/kir; Robinson et al.,
2010), variability in gene-content haplotypes is respon-
sible for significant diversity both within and between
populations.
In the last fifteen years, published reports have
described KIR gene-content frequency distributions in
more than 120 populations worldwide and are
available on the public database www.allelefrequen-
cies.net (Gonzalez-Galarza et al., 2011). However,
there have been limited studies examining these data
in aggregate to detect overall patterns of variation at
regional and global levels (Single et al., 2007; Middle-
ton et al., 2008; Hollenbach et al., 2010, 2012). The
KIR anthropology component (Population Global Dis-
tribution of KIR and Ligand) of the 15th and 16th
International Histocompatibility and Immunogenetics
Workshop (IHIW) have been intended to collect and
collate KIR and HLA frequency data in a diverse set
of human populations to more closely examine
worldwide variation in the KIR loci and the relation-
ship between KIR genes and their HLA ligands. Evi-
dence that KIR and HLA are co-evolving was first
demonstrated by Single et al. (2007); in the 15th
IHIW KIR Anthropology component, we presented
further support for this notion, finding a significant
correlation between KIR2DL2/L3 and its ligand,
HLA-C group 1(Hollenbach et al., 2010). A primary
aim of the 16th workshop project was to confirm and
extend this finding in additional worldwide popula-
tions.
During the course of the 15th IHIW project, fifteen
laboratories submitted KIR genotype and HLA ligand
* Children’s Hospital Oakland Research Institute, Oakland, CA,
USA, † Federal University of Parana, Curitiba, Brazil, ‡ Department
of Immunology & Immunogenetics, Instituto de Diagnostico y Refer-
encia Epidemiologicos (InDRE), Secretary of Health, Mexico City,
Mexico, § Russian Tissue Typing Center, Russian Research Institute
of Hematology and Transfusiology, St. Petersburg, Russia, ¶ Depart-
ment for Blood Group Serology & Transfusionsmedicine, University
of Vienna, Vienna, Austria, ∥ Institute of Integrative Biology, Univer-
sity of Liverpool, Liverpool, UK, ** Polish Academy of Sciences,
Wroclaw, Poland, †† Universit a di Roma ‘Tor Vergata’, Rome, Italy,
‡‡ London School of Hygiene & Tropical Medicine, London, UK,
§§ Karolinska Institutet, Huddinge, Sweden, ¶¶ Institute of Medical
Biology, Chinese Academy of Medical Sciences & Peking Union
Medical College, Kunming, China, ∥∥ Head Office, HLA Laboratory,
Canadian Blood Services, Ottawa, ON, Canada, *** Royal Liverpool
and Broadgreen University Hospital, Liverpool, UK and ††† Institute
of Infection and Global Health, University of Liverpool, Liverpool, UK
Received 23 October 2012; revised 6 November 2012; accepted 12
November 2012
Correspondence: Jill A. Hollenbach, Children’s Hospital Oakland
Research Institute, Oakland, CA, USA. Tel: 1 510 428 3885 X 5934;
Fax: 1 510 450 7920; E-mail: jhollenbach@chori.org
The data were contributed by 34 laboratories during the 4-year
course of this project, including data for the HGDP-CEPH popula-
tions. Additionally, data from the 15th IHIW and data contributed to
the allelefrequencies.net (AFND) database were combined with the
current workshop data set
© 2012 Blackwell Publishing Ltd
International Journal of Immunogenetics, 2013, 40, 39–45 39
doi: 10.1111/iji.12028