Killer Ig-like receptor (KIR) genotype and HLA ligand combinations in ulcerative colitis susceptibility

Abstract

Killer immunoglobulin-like receptors (KIRs) are expressed on natural killer cells and some T-cell subsets and produce either activation or inhibitory signals upon binding with the appropriate human leucocyte antigen (HLA) ligand on target cells. Recent genetic association studies have implicated KIR genotype in the development of several inflammatory conditions. Ulcerative colitis (UC) is an inflammatory disorder of the colonic mucosa that results from an inappropriate activation of the immune system driven by host bacterial flora. We developed a polymerase chain reaction-sequence specific primer (SSP)-based assay to genotype 194 UC patients and 216 control individuals for 14 KIR genes, the HLA-Cw ligand epitopes of the KIR2D receptors and a polymorphism of the lectin-like-activating receptor NKG2D. Initial analysis found the phenotype frequency of KIR2DL2 and -2DS2 to be significantly increased in the UC cohort (P ¼ 0.030 and 0.038, respectively). Logistic regression analysis revealed a protective effect conferred by KIR2DL3 in the presence of its ligand HLA-Cw group 1 (P ¼ 0.019). These results suggest that KIR genotype and HLA ligand interaction may contribute to the genetic susceptibility of UC.

Activating killer cell immunoglobulin-like receptor 2DS2 binds to HLA-A*11

“…Crystal structures of KIR2DL1-C*04:01 (10), KIR2DL2-C*03:04 (11), and KIR3DL1-B*57:01 (12) in complex with their respective HLA ligands are available, but there is as yet none for activating KIRs. The activating KIR 2DS2 is an interesting KIR that has been associated with NK responses and susceptibility to cytomegalovirus (13), hepatitis C virus (14), and ulcerative colitis (15). It has very close sequence similarity to KIR2DL2 and KIR2DL3, differing only in four and two amino acid residues, respectively, and, despite having only these few substitutions, binding to HLA-C was abrogated (16,17).…”

“…KIR3DL2 and KIR2DS4 have been reported to bind A*11 and that Lys44, Pro71, and Val72 are important for this interaction (15,16). Position 71 in KIR2DS2 is Gln71 and shows polar interaction with the Val76 backbone of A*11:01 (Fig.…”

An increased frequency of NK cell receptor and HLA-C group 1 combinations in early-onset type 1 diabetes

“…KIRs have been associated with a range of autoimmune conditions, such as psoriatic arthritis [12], rheumatoid arthritis [13], ulcerative colitis [14] and primary sclerosing cholangitis [15]. Results from genetic studies of KIRs in type 1 diabetes have been conflicting.…”

Overexpression of KIR inhibitory ligands (HLA-I) determines that immunosurveillance of myeloma depends on diverse and strong NK cell licensing

“…Gabriel's study did not describe any impact on PFS for KIR2DL1; however, authors showed that KIR2DL1 frequency was 94%, slightly higher than ours (86.8%), but lower than that described for British Caucasians (97.0 to 97.2%). 47,48 Differences in KIR2DL1 frequency between both series, in view of the rapid progressive disease observed for KIR2DL1…”