Killer Cell Immunoglobulin-Like Receptors (KIR) Typing by DNA Sequencing

Hou, Lihua; Chen, Minghua; Steiner, Noriko; Kariyawasam, Kanthi; Ng, Jennifer; Hurley, Carolyn Katovich

doi:10.1007/978-1-61779-842-9_25

Cited by 35 publications

(26 citation statements)

References 24 publications

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“…Briefly, testing for the presence or absence of specific KIR loci used polymerase chain reaction (PCR) amplification with visualization by agarose gel electrophoresis. To obtain a DNA sequence covering most of the coding regions of KIR2DL2/3 (31), several PCR primer pairs were used to generate three-four overlapping amplicons that were characterized by Sanger sequencing (31). Allele frequencies were calculated by gene counting.…”

Section: Methodsmentioning

confidence: 99%

Allelic Variation in KIR2DL3 Generates a KIR2DL2-like Receptor with Increased Binding to its HLA-C Ligand

Frazier

Steiner

Hou

et al. 2013

The Journal of Immunology

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Although extensive homology exists between their extracellular domains, natural killer cell inhibitory receptors KIR2DL2*001 and KIR2DL3*001 have previously been shown to differ substantially in their HLA-C binding avidity. To explore the largely uncharacterized impact of allelic diversity, the most common KIR2DL2/3 allelic products in European American and African American populations were evaluated for surface expression and binding affinity to their HLA-C group 1 and 2 ligands. Although no significant differences in the degree of cell membrane localization were detected in a transfected human NKL cell line by flow cytometry, surface plasmon resonance and KIR binding to a panel of HLA allotypes demonstrated that KIR2DL3*005 differed significantly from other KIR2DL3 allelic products in its ability to bind HLA-C. The increased affinity and avidity of KIR2DL3*005 for its ligand was also demonstrated to have a larger impact on the inhibition of IFN-γ production by the human KHYG-1 NK cell line compared to KIR2DL3*001, a low affinity allelic product. Site-directed mutagenesis established that the combination of arginine at residue 11 and glutamic acid at residue 35 in KIR2DL3*005 were critical to the observed phenotype. Although these residues are distal to the KIR/HLA-C interface, molecular modeling suggests that alteration in the interdomain hinge angle of KIR2DL3*005 towards that found in KIR2DL2*001, another strong receptor of the KIR2DL2/3 family, may be the cause of this increased affinity. The regain of inhibitory capacity by KIR2DL3*005 suggests that the rapidly evolving KIR locus may be responding to relatively recent selective pressures placed upon certain human populations.

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Section: Methodsmentioning

confidence: 99%

Allelic Variation in KIR2DL3 Generates a KIR2DL2-like Receptor with Increased Binding to its HLA-C Ligand

Frazier

Steiner

Hou

et al. 2013

The Journal of Immunology

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“…Donors were first screened using PCR methods previously described to identify donors potentially positive for KIR3DL1*009 (21, 25, 26). DNA samples from donors identified as positive for KIR3DL1*009 by PCR were subsequently evaluated by sequencing as previously described (27). …”

Section: Methodsmentioning

confidence: 99%

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

Mulrooney

Zhang

Goldgur

et al. 2015

The Journal of Immunology

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KIR3DL1 is a polymorphic inhibitory receptor that modulates natural killer 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 show that KIR3DL1*009 is expressed at a significantly lower surface density compared to KIR3DL1*001. Using recombinant proteins of KIR3DL1*001, KIR3DL1*009, and KIR3DS1*013 to analyze binding to HLA, we found that while KIR3DL1*009 displayed some evidence of binding to HLA compared to KIR3DS1*013, the binding was minimal compared to 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-positive NK cells exhibited less inhibition by HLA-Bw4 positive target cells compared to KIR3DL1*001-positive 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.

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“…The PCR and sequencing primers and conditions were as previously described (25). Sequencing reaction was performed using the ABI PRISM BigDye Terminator Cycle Sequencing Ready Reaction Kit.…”

Section: The Presence or Absence Of Kir Genesmentioning

confidence: 99%