Chain-terminating natural mutations affect the function of activating KIR receptors 3DS1 and 2DS3

Immunogenetics. 2007 Oct;59(10):779-92. doi: 10.1007/s00251-007-0239-1. Epub 2007 Jul 24.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • DNA Primers
  • Gene Expression Regulation / immunology
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Killer Cells, Natural / immunology*
  • Linkage Disequilibrium
  • Molecular Sequence Data
  • Mutation*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Receptors, KIR / genetics*
  • Receptors, KIR / immunology
  • Receptors, KIR3DS1 / genetics*
  • Receptors, KIR3DS1 / immunology
  • Sequence Analysis / methods*

Substances

  • DNA Primers
  • Histocompatibility Antigens Class I
  • KIR2DS3 protein, human
  • Receptors, KIR
  • Receptors, KIR3DS1