title: Chain-terminating natural mutations affect the function of activating KIR receptors 3DS1 and 2DS3.
abstract: To determine the nucleotide polymorphism of activating killer-cell immunoglobulin-like receptors (aKIR) 3DS1 and 2DS3, we developed a novel direct-sequencing method and analyzed DNA samples of 175 KIR3DS1(+) individuals and 72 KIR2DS3(+) individuals from the white population. The putative ligand-binding extracellular immunoglobulin (Ig)-like domains of these aKIR receptors are highly conserved, a scenario contrary to inhibitory KIRs that recognize polymorphic human leukocyte antigen (HLA) class I molecules. Null alleles 3DS1*049N and 2DS3*003N that do not express cell-surface receptors were discovered, and they occur commonly in whites (3DS1*049N = 2%; 2DS3*003N = 0.8%). Sequence-specific polymerase chain reaction (PCR) detecting these null alleles is negative with DNA from nonwhite subjects, suggesting that these null alleles are specific to whites and probably originated after the colonization of modern humans in Europe.
authors.affiliation: UCLA Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095-1652, USA.
authors.forename: Lihui
authors.initials: L
authors.lastname: Luo
authors.forename: Zeying
authors.initials: Z
authors.lastname: Du
authors.forename: Surendra K
authors.initials: SK
authors.lastname: Sharma
authors.forename: Rebecca
authors.initials: R
authors.lastname: Cullen
authors.forename: Stephen
authors.initials: S
authors.lastname: Spellman
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Reed
authors.forename: Raja
authors.initials: R
authors.lastname: Rajalingam
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D054340:Receptors, KIR / Q000235:genetics* / Q000276:immunology; D054349:Receptors, KIR3DS1 / Q000235:genetics* / Q000276:immunology; D017421:Sequence Analysis / Q000379:methods*
chemical_list: D017931:DNA Primers; D015395:Histocompatibility Antigens Class I; C541358:KIR2DS3 protein, human; D054340:Receptors, KIR; D054349:Receptors, KIR3DS1