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High-throughput killer cell immunoglobulin-like receptor genotyping by MALDI-TOF mass spectrometry with discovery of novel alleles
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High-throughput killer cell immunoglobulin-like receptor genotyping by MALDI-TOF mass spectrometry with discovery of novel alleles
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Journal Article
High-throughput killer cell immunoglobulin-like receptor genotyping by MALDI-TOF mass spectrometry with discovery of novel alleles
2007
Overview
The killer cell immunoglobulin-like receptors (KIR) interact with major histocompatibility complex (MHC) class I ligands to regulate the functions of natural killer cells and T cells. Like human leukocyte antigens class I, human KIR are highly variable and correlated with infection, autoimmunity, pregnancy syndromes, and transplantation outcome. Limiting the scope of KIR analysis is the low resolution, sensitivity, and speed of the established methods of KIR typing. In this study, we describe a first-generation single nucleotide polymorphism (SNP)-based method for typing the 17 human KIR genes and pseudogenes that uses analysis by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. It is a high-throughput method that requires minute amounts of genomic DNA for discrimination of KIR genes with some allelic resolution. A study of 233 individuals shows that the results obtained by the SNP-based KIR/MALDI-TOF method are consistent with those obtained with the established sequence-specific oligonucleotide probe or sequence-specific polymerase chain reaction methods. The added sensitivity of the KIR/MALDI-TOF method allowed putative novel alleles of the KIR2DL1, KIR3DL1, KIR2DS5, and KIR2DL5 genes to be identified. Sequencing the KIR2DL5 variant proved it was a newly discovered allele, one that appears associated with Hispanic and Native American populations. This KIR/MALDI-TOF method of KIR typing should facilitate population and disease-association studies that improve knowledge of the immunological functions of KIR-MHC class I interactions.
Publisher
Berlin/Heidelberg : Springer-Verlag,Springer Nature B.V
Subject
/ Antigens
/ Genes
/ Genotype
/ HLA
/ Humans
/ Immunoglobulin-like receptors
/ Killer cell immunoglobulin-like receptors
/ Killer Cells, Natural - chemistry
/ Killer Cells, Natural - immunology
/ Killer Cells, Natural - metabolism
/ KIR
/ Major histocompatibility complex
/ Polymorphism, Single Nucleotide
/ Potassium channels (inwardly-rectifying)
/ Receptors, Immunologic - chemistry
/ Receptors, Immunologic - genetics
/ Single-nucleotide polymorphism
/ SNP
/ Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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