Diversity of the KIR gene cluster in an urban Brazilian population

Abstract

The activity of natural killer cells depends on the balance between activating and inhibitory signals coming from their receptors. Among these are the killer cell immunoglobulin-like receptors (KIR) that recognize specific HLA class I allotypes. Here we characterized KIR genetic diversity and their HLA ligands in the population of Curitiba, Paraná State (n=164), and compared it with other worldwide populations. The distribution of 2DL4 alleles was also analyzed. The Curitiba population did not differ significantly from European and Euro-descendant populations, but as an admixed population showed higher genetic diversity. We found 27 KIR profiles, many of them uncommon in European populations, in agreement with the elevated historically recent gene flow in the study population. The frequencies of KIR genes and their respective HLA ligands were distributed independently and none of the analyzed individuals lacked functional KIR–HLA ligand combinations. KIR gene frequencies of 33 worldwide populations were consistent with geographic and ethnic distribution, in agreement with demography being the major factor shaping the observed gene content diversity of the KIR locus.

KIR Gene Content in Amerindians Indicates Influence of Demographic Factors

“…Yet the fact that the difference between observed and expected frequencies of KIR genes and their HLA ligands in the present study was close to zero indicates that the selection pressure at least at this level is low. We reported a similar conclusion when analyzing a Brazilian urban population [11].…”

“…KIR3DL1 recognizes HLA-B and HLA-A molecules with the Bw4 epitope [8] and it has been suggested that KIR3DS1 also binds the Bw4 epitope [9], [10]. Although HLA-B epitopes are currently considered the most important KIR3DL1/S1 ligands, we recently suggested that both HLA-A and B allotypes may be equally important for NK function [11], which corroborates the suggestion about HLA-A and HLA-B having compensatory function in the engagement of KIR receptors and being a KIR-driven functional genetic block [12].…”

16th IHIW: Population Global Distribution of Killer Immunoglobulin‐like Receptor (KIR) and Ligands

“…We contribute with two samples for this workshop: Curitiba ( n = 162) is from Southern Brazil (Curitiba, Parana State) of predominantly European ancestry, and its KIR diversity was already reported (Augusto et al ., ,b;); the second one, Campo Grande ( n = 205) from Western Brazil. This population is extensively mixed by European and African ancestries, but also there is a significant Amerindian component.…”

A deep look at KIR–HLA in Amerindians: Comprehensive meta-analysis reveals limited diversity of KIR haplotypes

“…[53,54]. We have previously suggested that although KIR2DL2 313 binds HLA-C ligands with higher affinity than KIR2DL3 [55], relax- Recently, we suggested that both HLA-A and HLA-B could be 342 equally important for KIR recognition [41]. In a remarkable study, 343 Capittini et al [63] …”

“…Amerindians exhibits a low 40 diversity of KIR gene-content haplotypes when compared to most worldwide population. We compared 41 the KIR-HLA diversity within and between Amerindian groups trying to understand the natural causes of 1. Introduction 51 Killer-cell immunoglobulin-like receptors (KIR) are expressed 52 on the surface of natural killer (NK) cells.…”