Dataset Information


KIR3DS1-Specific D0 Domain Polymorphisms Disrupt KIR3DL1 Surface Expression and HLA Binding.

ABSTRACT: KIR3DL1 is a polymorphic inhibitory receptor that modulates NK cell activity through interacting with HLA-A and HLA-B alleles that carry the Bw4 epitope. Amino acid polymorphisms throughout KIR3DL1 impact receptor surface expression and affinity for HLA. KIR3DL1/S1 encodes inhibitory and activating alleles, but despite high homology with KIR3DL1, the activating receptor KIR3DS1 does not bind the same ligand. Allele KIR3DL1*009 resulted from a gene recombination event between the inhibitory receptor allele KIR3DL1*001 and the activating receptor allele KIR3DS1*013. This study analyzed the functional impact of KIR3DS1-specific polymorphisms on KIR3DL1*009 surface expression, binding to HLA, and functional capacity. Flow-cytometric analysis of primary human NK cells as well as transfected HEK293T cells shows that KIR3DL1*009 is expressed at a significantly lower surface density compared with KIR3DL1*001. Using recombinant proteins of KIR3DL1*001, KIR3DL1*009, and KIR3DS1*013 to analyze binding to HLA, we found that although KIR3DL1*009 displayed some evidence of binding to HLA compared with KIR3DS1*013, the binding was minimal compared with KIR3DL1*001 and KIR3DL1*005. Mutagenesis of polymorphic sites revealed that the surface phenotype and reduced binding of KIR3DL1*009 are caused by the combined amino acid polymorphisms at positions 58 and 92 within the D0 extracellular domain. Resulting from these effects, KIR3DL1*009(+) NK cells exhibited significantly less inhibition by HLA-Bw4(+) target cells compared with KIR3DL1*001(+) NK cells. The data from this study contribute novel insight into how KIR3DS1-specific polymorphisms in the extracellular region impact KIR3DL1 surface expression, ligand binding, and inhibitory function.

SUBMITTER: Mulrooney TJ 

PROVIDER: S-EPMC4506867 | BioStudies | 2015-01-01

REPOSITORIES: biostudies

Similar Datasets

2011-01-01 | S-EPMC3159812 | BioStudies
2017-01-01 | S-EPMC5445109 | BioStudies
2014-01-01 | S-EPMC4201542 | BioStudies
2015-01-01 | S-EPMC4442525 | BioStudies
2013-01-01 | S-EPMC3741655 | BioStudies
2015-01-01 | S-EPMC4282956 | BioStudies
2012-01-01 | S-EPMC3485674 | BioStudies
2013-01-01 | S-EPMC3766012 | BioStudies
2011-01-01 | S-EPMC3226550 | BioStudies
2013-01-01 | S-EPMC3747338 | BioStudies