Balkan Journal of Medical Genetics

KIR AND HLA HAPLOTYPE ANALYSIS IN A FAMILY LACKING THE KIR 2DL1-2DP1 GENES
Vojvodić S, Ademović-Sazdanić D
*Corresponding Author: Associate Professor Svetlana Vojvodić, Institute for Blood Transfusion of Vojvodina, Tissue Typing Compartment, Medical Faculty of the University of Novi Sad, Hajduk Veljkova 9a, 21000 Novi Sad, Serbia; Tel: +381-21-4877-963, Fax: +381-21-4877-978; E-mail: svetlana.vojvodic021@gmail.com
page: 55

INTRODUCTION

Natural killer (NK) cells of innate immunity and CD8+ cytotoxic T cells (CTL) of adaptive immunity are professional killer cells that are necessary for defense against virus-infected or tumor-transformed cells. Natural killer cells recognize and kill target cells with absent or altered expression of human leukocyte antigen (HLA) class I molecules. This missing self recognition makes NK cells able to eliminate tumoral and virus-infected cells that lack self HLA class I molecules. Furthermore, in the allogeneic context of hematopoietic stem cell transplantation, NK cells from the donor can be alloreactive against recipient cells. This NK cell alloreactivity is mediated by a balance between activating and inhibitory signals and leads to cytotoxicity and production of proinflammatory cytokines, such as IFN-γ. Receptors of HLA class I molecules involved in recognition of target cells partly belong to the killer cell Ig-like receptor (KIR) family, encoded by 14 genes and two pseudogenes located on chromosome 19q13.4, within a 100 to 200 kb region of the leukocyte receptor complex (LRC) [1-5]. The number of genes present in KIR haplotypes is variable, however four genes (KIR 3DL3, KIR3DP1, KIR2DL4, KIR3DL2) are present on virtually all haplotypes, and are thus considered as framework genes. Two major classes of KIR haplotypes (A and B) have been identified, which is unique to the human species and that were shown to have differential associations with disease and reproductive success. The A haplotype contains four genes in addition to the framework genes (KIR2DL1, KIR2DL3, KIR3DL1, KIR2DS4), representing a predominantly inhibitory haplotype. There are many B haplotypes, containing various combinations of the activating KIR genes [1-3,6-9]. In addition to the substantial variation in gene content across haplotypes, each KIR gene itself exhibits considerable nucleotide sequence polymorphism explaining why the genomic diversity of the human KIR gene family is its important characteristic attributed to the variability in both gene numbers and allelic polymorphism [7,9-11]. Every KIR haplotype is a combination of a centromeric and a telomeric KIR gene motif. DNA sequencing of single copies of chromosome 19 [8,12] and family segregation analysis [13,14] have defined three common centromeric (Cen-A1, Cen-B1, Cen-B2) and two common telomeric (Tel-A1 and Tel-B1) haplotype structures based on the presence and absence of specific KIR genes. As examples, Cen-A1 is comprised of KIR3DL3~KIR2DL3~KIR2DP1~KIR2DL1~KIR 3DP1 in this gene order, whereas Tel-A1 includes KIR2DL4~ KIR3DL1~KIR2DS4~KIR3DL2. In this report, we present a detailed HLA and KIR haplotype analysis of a family having rare KIR genotype. All members of the family described here displayed a greater degree of diversity of KIR genetic profiles, that indicates further complexity of underlying haplotypes; in this respect, we described six individuals (grandfather, mother, father and three offspring), who possess an incomplete KIR haplotype with the 3DP1 variant allele (due to lack of 2DP1-2DL1 alleles). The aim of the presented case study was to determine possible explanation of rare KIR genotype present in patient, siblings and parents of the patient, through the segregation KIR analysis in patient’s grandfather and grandmothers.

Number 25 VOL. 25 (1), 2022	Number 24 VOL. 24(2), 2021
Number 24 VOL. 24(1), 2021	Number 23 VOL. 23(2), 2020
Number 22 VOL. 22(2), 2019	Number 22 VOL. 22(1), 2019
Number 22 VOL. 22, 2019 Supplement	Number 21 VOL. 21(2), 2018
Number 21 VOL. 21 (1), 2018	Number 21 VOL. 21, 2018 Supplement
Number 20 VOL. 20 (2), 2017	Number 20 VOL. 20 (1), 2017
Number 19 VOL. 19 (2), 2016	Number 19 VOL. 19 (1), 2016
Number 18 VOL. 18 (2), 2015	Number 18 VOL. 18 (1), 2015
Number 17 VOL. 17 (2), 2014	Number 17 VOL. 17 (1), 2014
Number 16 VOL. 16 (2), 2013	Number 16 VOL. 16 (1), 2013
Number 15 VOL. 15 (2), 2012	Number 15 VOL. 15, 2012 Supplement
Number 15 Vol. 15 (1), 2012	Number 14 14 - Vol. 14 (2), 2011
Number 14 The 9th Balkan Congress of Medical Genetics	Number 14 14 - Vol. 14 (1), 2011
Number 13 Vol. 13 (2), 2010	Number 13 Vol.13 (1), 2010
Number 12 Vol.12 (2), 2009	Number 12 Vol.12 (1), 2009
Number 11 Vol.11 (2),2008	Number 11 Vol.11 (1),2008
Number 10 Vol.10 (2), 2007	Number 10 10 (1),2007
Number 9 1&2, 2006	Number 9 3&4, 2006
Number 8 1&2, 2005	Number 8 3&4, 2004
Number 7 1&2, 2004	Number 6 3&4, 2003
Number 6 1&2, 2003	Number 5 3&4, 2002
Number 5 1&2, 2002	Number 4 Vol.3 (4), 2000
Number 4 Vol.2 (4), 1999	Number 4 Vol.1 (4), 1998
Number 4 3&4, 2001	Number 4 1&2, 2001
Number 3 Vol.3 (3), 2000	Number 3 Vol.2 (3), 1999
Number 3 Vol.1 (3), 1998	Number 2 Vol.3(2), 2000
Number 2 Vol.1 (2), 1998	Number 2 Vol.2 (2), 1999
Number 1 Vol.3 (1), 2000	Number 1 Vol.2 (1), 1999
Number 1 Vol.1 (1), 1998

About the journal ::: Editorial ::: Subscription ::: Information for authors ::: Contact