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KIR2DL5 alleles mark certain combination of activating KIR genes

Genes & Immunity volume 9, pages 470–480 (2008)Cite this article

Abstract

Killer cell Ig-like receptors (KIR) control the immune response of NK cells and some T cells to infections and tumors. KIR genes evolve rapidly and are variable between individuals in their number, type and sequence. Here, we determined the nature of KIR2DL5 gene polymorphism in four ethnic groups using direct DNA sequencing method. Nine new sequences were discovered. Within the panel of 248 KIR2DL5-positive individuals, 14 KIR2DL5-sequences differing in coding regions were observed. They differed at only seven amino acid positions, and such limited polymorphism is consistent with its conserved nature throughout the hominoid lineage. Ethnic deviation was seen in the distribution of KIR2DL5A, KIR2DL5B and their alleles. African Americans had more KIR2DL5 alleles than other populations indicating that more polymorphisms are yet to be discovered in Africans. Linkage between KIR2DL5-alleles and certain activating-KIR genes were observed, but frequency of these linked clusters differed substantially between populations. Consequently, KIR2DL5 alleles can be used as markers to predict the activating-KIR gene content. Typing system distinguishing A*001 and B*002 alleles can serve as a powerful screening test to assess the content of most variable activating-KIR genes that have been implicated in human disease and in the outcome of hematopoietic stem cell transplantation.

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Acknowledgements

This work was supported by start-up funds from the UCLA Department of Pathology and Laboratory Medicine to Dr Rajalingam, and by funding from the National Marrow Donor Program (NMDP) and the Department of the Navy, Office of Naval Research Cooperative Agreement no. N00014-99-2-0006 and Grant no. N00014-05-1-0859 to the NMDP. We thank Damian Goodridge, Conexio Genomics, Western Australia for his help in building and optimizing KIR sequence libraries for the use in Assign software, John Muramoto for providing DNA samples from the UCLA International DNA Exchange Program, and Cynthia Vierra-Green and Rebecca Cullen for providing DNA samples from the NMDP repository. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the Office of Naval Research or the NMDP.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, UCLA Immunogenetics Center, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA

    Z Du, E F Reed & R Rajalingam

  2. Department of Medicine, All India Institute of Medical Sciences, New Delhi, India

    S K Sharma

  3. National Marrow Donor Program (NMDP), Minneapolis, MN, USA

    S Spellman

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  1. Z Du
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Correspondence to R Rajalingam.

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Du, Z., Sharma, S., Spellman, S. et al. KIR2DL5 alleles mark certain combination of activating KIR genes. Genes Immun 9, 470–480 (2008). https://doi.org/10.1038/gene.2008.39

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Keywords

  • killer cell immunoglobulin-like receptor
  • KIR2DL5
  • NK cell receptors
  • polymorphism
  • population diversity

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