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The novel KIR2DL3*00112 allele differs from the closest allele KIR2DL3*00101 by a single same sense mutation., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

KIR2DL2 and KIR2DL3 segregate as alleles of the same killer cell immunoglobulin-like receptor (KIR) gene locus. They have been associated with viral infectious diseases and certain cancers and their allelic information may help to better comprehend mechanisms. The allelic polymorphism of KIR2DL2/2DL3 has been shown to influence their binding specificity and affinity to the HLA-C1 ligands. The present study aims to investigate the distribution of the allelic polymorphism of KIR2DL2/2DL3 in a southern Chinese population using sequence-specific primer polymerase chain reaction (PCR-SSP) and PCR-sequence-based typing (SBT) at the entire coding sequence. Of the 306 tested individuals, 1.96% were positive for KIR2DL2 only, 78.10% for KIR2DL3 only, and 19.93% for both KIR2DL2 and 2DL3. KIR2DL3 showed a high degree of diversity in the study population with 15 alleles detected including 8 novel ones. The predominant 2DL3 allele in the study population is 2DL3*00101 (92.81%) followed by 2DL3*00201 (24.18%), 2DL3*023 (4.25%), and 2DL3*00109 (1.31%). The remaining 11 2DL3 alleles all had a frequency below 1%. Three detected 2DL2 alleles were 2DL2*00301 (18.95%), 2DL2*00101 (3.59%), and the novel 2DL2*013 (0.33%). These results provide further insight into the KIR gene diversity in Southern Chinese and may help to better understand the role played by KIR genes in associated diseases., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel 2DL3*032 allele differs from the closest allele KIR2DL3*0010101 by a non-synonymous mutation in exon 7., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

KIR2DL3*026 differs from the closest allele KIR2DL3*00101 by a nonsynonymous mutation in exon 4., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

KIR2DL3*027 differs from the closest allele KIR2DL3*00101 by a nonsynonymous mutation in exon 7., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

KIR2DL3*029 differs from the closest allele KIR2DL3*00101 by a single missense mutation at CDS nt505 C > A., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel KIR2DL3*025 allele differs from the closest allele KIR2DL3*0010101 by a non-synonymous mutation at CDS nt280 C>A in exon 4., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

KIR2DL3*030 differs from the closest allele, KIR2DL3*00101, by a single missense mutation at CDS., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

KIR2DL3*00110 differs from KIR2DL3*00101 by a single silent mutation at coding sequence (CDS) nt618 A>C in exon 5., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel KIR2DL3*031 allele differs from KIR2DL3*00101 by a synonymous mutation and a non-synonymous mutation., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We report four novel KIR2DL2 alleles and two novel KIR2DL3 alleles identified from an East African population using sequence-based typing. Sequencing and molecular cloning of exon 4 confirmed that the new 2DL2 alleles were identical to 2DL2*003, except for the following nucleotide differences: 2DL2*00601 had a difference at codon 16 (CGC→CCC), resulting in a coding change from arginine to proline; 2DL2*00602 also had this difference at codon 16, as well as a synonymous difference (GAT→GAC) at codon 31; 2DL2*00303 had a synonymous difference (AAA→AAG) at codon 61; and 2DL2*00304 had a synonymous difference (GGG→GGA) at codon 75. 2DL3*017 was identical to 2DL3*005 except at codon 11 (CGG→CTG, arginine→leucine) and exon 9, codons 297 (CAC→CGC, histidine→arginine) and 321 (TGA→AGA, stop codon→arginine). 2DL3*00104 was identical to KIR2DL3*001 except for a synonymous difference (GAG→GAA) at codon 54. Identification of novel killer cell immunoglobulin-like receptor (KIR) alleles is a testament to the genetic diversity in this population., (Copyright © 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

In humans, recent clinical and experimental data from hematopoietic stem cell transplantation revealed that donor-derived alloreactive NK cells exert a beneficial graft versus leukemia effect. The existence of donor-derived alloreactive NK cells can be predicted on the basis of donor killer cell Ig-like receptor (KIR) gene profile and HLA class I typing of both donor and recipient. Moreover, the size of the alloreactive NK cell population can be directly assessed by the combined use of anti-KIR-specific mAb. In this study, in an attempt to improve the definition of alloreactive NK cell subsets, we assessed the KIR genotype and phenotype in a cohort of 44 donors. This approach allowed the identification of two different KIR2DL3 alleles (KIR2DL3*005 and the novel allele KIR2DL3*015) that did not react with the anti-KIR2DL3-specific ECM41 mAb. In contrast, both alleles were recognized at the cell surface by several mAb reacting with KIR2DL2/L3/S2. Notably, KIR2DL3*005 was also stained by the anti-KIR2DL1/S1-specific EB6B and 11PB6 mAb. Functional analysis revealed that, despite its particular mAb reactivity, the specificity of KIR2DL3*005 for HLA-C molecules did not differ from that of other KIR2DL2/L3 alleles. Finally, site-directed mutagenesis demonstrated that glutamine at position 35 is required for ECM41 staining, whereas glutamic acid 35 and arginine 50 are relevant for staining with EB6B or 11PB6 mAb. Our present data represent a substantial progress in the characterization of the NK cell repertoire and an improved phenotypic/functional definition of given KIR(+) subsets.