Original Article

Genes and Immunity (2008) 9, 470–480; doi:10.1038/gene.2008.39; published online 29 May 2008

KIR2DL5 alleles mark certain combination of activating KIR genes

Z Du1, S K Sharma2, S Spellman3, E F Reed1 and R Rajalingam1

  1. 1Department 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
  2. 2Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
  3. 3National Marrow Donor Program (NMDP), Minneapolis, MN, USA

Correspondence: Dr R Rajalingam, Department of Pathology and Laboratory Medicine, UCLA Immunogenetics Center, David Geffen School of Medicine at UCLA, University of California at Los Angeles, 1000 Veteran Avenue, Room no. 1–536, Box: 951652, Los Angeles, CA 90095-1652, USA. E-mail: rrajalingam@mednet.ucla.edu

Received 19 March 2008; Revised 23 April 2008; Accepted 25 April 2008; Published online 29 May 2008.

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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.

Keywords:

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

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