KIR in type 1 diabetes: disparate distribution of activating and inhibitory natural killer cell receptors in patients versus HLA-matched control subjects.
Killer cell immunoglobulin-like receptors (KIRs) modulate natural killer cell and T-cell function by interacting with HLA class 1 ligands on target cells. Both KIR and HLA are highly polymorphic. We studied the influence of KIR and HLA class 1 genes on the susceptibility to develop type 1 diabetes. The results showed increased numbers of activating KIR genes in patients compared with control subjects (P = 0.049). The combination of the activating KIR2DS2 gene, together with its putative HLA ligand, was present more frequently in patients than in diabetes high-risk HLA-matched control subjects (P = 0.030). Moreover, our results imply that an increase in activating KIR2DS2-HLA ligand pairs combined with a lack of inhibitory KIR-HLA ligand pairs is associated with an additional risk to develop type 1 diabetes in individuals with diabetes high-risk HLA alleles (P = 0.035). We propose that the genetic imbalance between KIR and their HLA class 1 ligands may enhance the activation of T-cells with a low affinity for pancreatic self-antigens, thereby contributing to the pathogenesis of type 1 diabetes.
D000293:Adolescent; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism*; D008024:Ligands; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D054340:Receptors, KIR; D014018:Tissue Distribution
D015395:Histocompatibility Antigens Class I; C433932:KIR2DS2 protein, human; D008024:Ligands; D011971:Receptors, Immunologic; D054340:Receptors, KIR