HLA ISSN 2059-2302 BRIEF COMMUNICATION KIR genotypic diversity in Portuguese and analysis of KIR gene allocation after allogeneic hematopoietic stem cell transplantation D. Ligeiro 1 , S. Buhler 2,3 , M. Abecasis 4 , O. Abade 1 , A. Sanchez-Mazas 2,5 , M. Gomes da Silva 4,6 & H. Trindade 1 1 Lisbon Center for Blood and Transplantation, Instituto Português de Sangue e Transplantação, Lisbon, Portugal 2 Laboratory of Anthropology, Genetics and Peopling History, Department of Genetics and Evolution-Anthropology Unit, University of Geneva, Geneva, Switzerland 3 Transplantation Immunology Unit & National Reference Laboratory for Histocompatibility, Department of Genetic and Laboratory Medicine, Geneva University Hospital, Geneva, Switzerland 4 Hematology Department, Instituto Português de Oncologia de Lisboa, Francisco Gentil, EPE, Lisbon, Portugal 5 Institute of Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland 6 CEDOC, NOVA Medical School, Universidade Nova de Lisboa, Lisbon, Portugal Key words hematopoietic stem cell transplantation; killer immunoglobulin-like receptors genotypic diversity; killer immunoglobulin-like receptors–human leukocyte antigen ligand interaction; natural killer cell alloreactivity Correspondence Dario Ligeiro Lisbon Center for Blood and Transplantation IPST-IP Alameda Linhas de Torres 117 1169-001 Lisbon Portugal Tel: 00351217504100 Fax: 00351217504142 e-mail: dario@ipst.min-saude.pt Received 16 October 2015; revised 20 January 2016; accepted 8 March 2016 doi: 10.1111/tan.12795 Abstract The diversity of killer-cell immunoglobulin-like receptors (KIR) genes was evaluated in Portuguese and the observed genotypic profles were found related to the ones reported in European populations. The KIR repertoire after hematopoietic stem cell transplantation is determined by these gene frequencies and the KIR group B motifs are the less common. We estimated donor–KIR/recipient–ligand interactions in transplants with related donors and unrelated donors found in a local registry or from abroad. A large fraction of transplants had all three ligands of inhibitory receptors, and therefore, in theory were not prone to natural killer cell (NK) mediated alloreactivity. Furthermore, the distribution of KIR alloreactive interactions was found independent of the donor–recipient genetic proximity, probably because of different gene segregation and comparable KIR frequencies in the donor pools. Introduction The function of mature natural killer (NK) cells is under the dominant control of a repertoire of inhibitory receptors, stochastically expressed, that comprises the variable killer-cell immunoglobulin-like receptors (KIR) family (1). These recep- tors recognize specifc forms of human leukocyte antigen (HLA) class I molecules as markers of self in normal cells (2) and a ligand compromised expression allows a large group of activating NK receptors and co-receptors to trigger cytolytic activity (3, 4). Several layers of complexity contribute to KIR extensive genetic and cellular diversity, including variable gene types and content, allelic polymorphism, the combination of inherited haplotypes and a variegated clonal expression (5, 6). At present, a cluster of 16 KIR genes have been characterized in humans, of which 8 are NK cell inhibitors (KIR2DL1–5, 3DL1–3), 6 NK cell activators (KIR2DS1–5, 3DS1) and 2 pseudogenes (KIR2DP1, 3DP1). The genomic structure of KIR haplotypes is defned by a framework of conserved genes located at the centromeric (3DL3) and telomeric (3DL2) ends, as well as in the central part (3DP1 and 2DL4) (7). These framework genes defne two regions; a centromeric, with two alternative gene-content motifs named Cen-A and Cen-B and a telomeric, also with two types of contents, named Tel-A and Tel-B. Cen-A and Tel-A combine to each other to form rel- atively short haplotypes named group A KIR haplotypes. All other motif combinations, i.e. Cen-B with Tel-B, Cen-B with Tel-A, and Cen-A with Tel-B are collectively called group B KIR haplotypes (8). The main distinction between group A and group B haplotypes is in the number of activator KIR genes. Group A haplotypes contain at most a single activator gene, © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 375 HLA, 2016, 87, 375–380