Genotypic diversity of the Killer Cell Immunoglobulin-like Receptors (KIR) and their HLA class I Ligands in a Saudi population

Abstract

Killer Cell Immunoglobulin-like Receptors (KIR) have been used as good markers for the study of genetic predisposition in many diseases and in human genetic population dynamics. In this context, we have investigated the genetic diversity of KIR genes and their main HLA class I ligands in Saudi population and compared the data with other studies of neighboring populations. One hundred and fourteen randomly selected healthy Saudi subjects were genotyped for the presence or absence of 16 KIR genes and their HLA-C1, -C2, -Bw4Thr80 and Bw4Ile80 groups, using a PCR-SSP technique. The results show the occurrence of the framework genes (3DL2, 3DL3 and 2DL4) and the pseudogenes (2DP1 and 3DP1) at highest frequencies. All inhibitory KIR (iKIR) genes appeared at higher frequencies than activating genes (aKIR), except for 2DS4 with a frequency of 90.35%. A total of 55 different genotypes were observed appearing at different frequencies, where 12 are considered novel. Two haplotypes were characterized, AA and Bx (BB and AB), which were observed in 24.5% and 75.5% respectively of the studied group. The frequencies of iKIR + HLA associations were found to be much higher than aKIR + HLA. KIR genes frequencies in the Saudi population are comparable with other Middle Eastern and North African populations.

Spectrum and Frequency of Nk Cell Receptor Genes Among Cystic Fibrosis Patients

“…As can be seen from the results presented, the KIR genes of the inhibitory receptors were more frequent in the control group than the activation receptor genes. The results we get are in common with the results of other researchers [7,11,17,18]. It should be noted, that the primary in evolutionary point of view are the inhibitory receptors of NK cells, whose role was to inhibit the cytotoxic activity of natural killer cells, in particular, with regard to the cells of their own organism.…”

“…KIRs are transmembrane glycoproteins with two or three extracellular immunoglobulin-like domains (KIR2D and KIR3D, respectively) and a long (L) or short (S) cytoplasmic tail. Receptors with L-tail carry out an inhibitory signal, and with S-tail -activating [7,8].…”

Daratumumab augments alloreactive natural killer cell cytotoxicity towards CD38+ multiple myeloma cell lines in a biochemical context mimicking tumour microenvironment conditions

“…In the current study, we demonstrate that selection of a donor based on HLA genotype and KIR expression could be a good way to achieve a KIR-ligand mismatched status to minimize the detrimental effects of KIR/HLA. Selection of KIR-ligand mismatched donors would be feasible for allogeneic NK cell treatments where the patient lacks at least one of the HLA epitopes binding to inhibitory KIRs, as is the case in approximately 70% of the individuals (Mahaweni unpublished data and [ 35 ]). Also in the situation where a glycoengineered antibody is used, selection of a KIR-ligand mismatched donor could be beneficial since tumor cells could downregulate the expression of the antigen targeted by the antibody.…”

Genetic polymorphism and evolutionary differentiation of Eastern Chinese Han: a comprehensive and comparative analysis on KIRs

“…KIR2DL4 has both inhibitory and active functions 12 . Among all KIR genes, four genes KIR2DL4, KIR3DL2, KIR3DL3 and KIR3DP1 are described as framework genes, and they are present in nearly all individuals 15 .…”