title: Effects of NKG2D haplotypes on the cell-surface expression of NKG2D protein on natural killer and CD8 T cells of peripheral blood among atomic-bomb survivors.
abstract: NKG2D is a primary activating receptor that triggers cell-mediated cytotoxicity in NK cells against tumor and virus-infected cells. We previously identified the NKG2D haplotypes in the natural killer gene complex region on chromosome 12p. Two major haplotype alleles, LNK1 and HNK1, were closely related to low and high natural cytotoxic activity phenotypes, respectively. Furthermore, the haplotype of HNK1/HNK1 has revealed a decreased risk of cancer compared with LNK1/LNK1. In the present study, using flow cytometry, we evaluated the functional effects of NKG2D haplotypes and five htSNPs in terms of the cell-surface expression of NKG2D protein on NK and CD8 T cells of peripheral blood among 732 atomic-bomb survivors. NKG2D expression on NK cells showed significant increases, in the order of LNK1/LNK1, LNK1/HNK1 and HNK1/HNK1 haplotypes (p for trend=0.003), or with major homozygous, heterozygous, and minor homozygous genotypes for individual htSNPs (p for trend=0.02-0.003). The same trend was observed for NKG2D expression on CD8 T cells. Our findings indicate that the NKG2D haplotypes are associated with the expression levels of NKG2D protein on NK and CD8 T cells, resulting in inter-individual variations in human cytotoxic response.
authors.affiliation: Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan. kimai@rerf.or.jp
authors.forename: Kazue
authors.initials: K
authors.lastname: Imai
authors.forename: Tomonori
authors.initials: T
authors.lastname: Hayashi
authors.forename: Mika
authors.initials: M
authors.lastname: Yamaoka
authors.forename: Junko
authors.initials: J
authors.lastname: Kajimura
authors.forename: Kengo
authors.initials: K
authors.lastname: Yoshida
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kusunoki
authors.forename: Kei
authors.initials: K
authors.lastname: Nakachi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000528:radiation effects; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics / Q000528:radiation effects; D005260:Female; D005434:Flow Cytometry; D005720:Gamma Rays / Q000009:adverse effects; D015870:Gene Expression / Q000528:radiation effects; D005787:Gene Frequency; D014644:Genetic Variation; D006239:Haplotypes / Q000528:radiation effects; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism* / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics* / Q000276:immunology; D009369:Neoplasms / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D054043:Nuclear Weapons; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics* / Q000276:immunology; D012306:Risk; D017741:Survivors
chemical_list: C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K