Protective Effect of the HLA‐Bw4I80 Epitope and the Killer Cell Immunoglobulin‐Like Receptor 3DS1 Gene against the Development of Hepatocellular Carcinoma in Patients with Hepatitis C Virus Infection

Abstract

The aim of the present study was to investigate, in 152 Spanish patients infected with hepatitis C virus (HCV), the possibility that killer cell immunoglobulin-like receptors (KIRs) influence progression to hepatocellular carcinoma. KIRs are related to the activation and inhibition of natural killer cells and may play an important role in the innate response against infection with such viruses as HCV. We found that the human leukocyte antigen-Bw4I80 epitope and the KIR3DS1 gene were more frequent in HCV carriers than in patients with hepatocellular carcinoma. Moreover, these associations were not independent of each other-the KIR3DS1/Bw4I80 genotype clearly was also more frequent in HCV carriers (odds ratio, 24.22).NK cells provide defense against viral infections by producing cytokines and causing cytotoxicity, and this capacity is dependent on an equilibrium between the inhibitory and activating receptors [1]. The killer cell immunoglobulin-like receptor (KIR) genes encode a group of proteins that are expressed on NK cells and some T cells [2]. These genes are located on chromosome 19q13.4 in the leukocyte receptor complex. KIR proteins act as receptors that recognize major histocompatibility

Ly49 cluster sequence analysis in a mouse model of diabetes: an expanded repertoire of activating receptors in the NOD genome

“…Individuals with HIV or HCV that express KIR3DS1 and HLA-B Bw4-80Ile are protected from disease progression. 47,48 Although the high number of activating Ly49 in NOD mice is consistent with the hypothesis that activating class I MHC receptors contribute to autoimmune disease incidence, the assumed strong anti-viral protective effect of many activating Ly49 is not found when NOD mice are challenged with MCMV ( Figure 8c). This is despite the presence of two Ly49h-and two Ly49p-related genes.…”

Phenotypic and Functional Analyses of KIR3DL1+ and KIR3DS1+ NK Cell Subsets Demonstrate Differential Regulation by Bw4 Molecules and Induced KIR3DS1 Expression on Stimulated NK Cells

“…Indeed, HLA-Bw4 tetramers loaded with various peptides did not succeed in binding to KIR3DS1 (22). This absence of interaction in vitro does not exclude protection by the KIR3DS1-Bw4 association as suggested by genetic studies for the acute hepatitis C virus (23,24), the human papillomavirus (25,26), and HIV-1 infections (27)(28)(29). The recent findings showing that KIR3DS1 is actually expressed on the cell surface and is detectable by flow cytometry with the KIR3DL1/S1-specific mAb, Z27, at a very low intensity of fluorescence (30 -33), led to study KIR3DS1 expression and to investigate a potential interaction between KIR3DS1 and HLA-Bw4.…”

The potential influence of KIR cluster profiles on disease patterns of Canadian Aboriginals and other indigenous peoples of the Americas

“…This cellular regulation can influence the course of infections, autoimmunity, cancers and other diseases. [1][2][3][4][5] The KIR cluster contains 15 genes and 2 pseudogenes, 6 which are segregated within the centromeric and telomeric portions of the cluster. The centromeric and telomeric regions are flanked by framework genes KIR3DL3 and KIR3DL2, respectively.…”