Receptor-ligand analyses define minimal killer cell Ig-like receptor (KIR) in humans

Immunogenetics. 2007 Jan;59(1):1-15. doi: 10.1007/s00251-006-0168-4. Epub 2006 Nov 14.

Abstract

Interactions between inhibitory killer cell immunoglobulin-like receptors (iKIR) and human leukocyte antigen (HLA) class I molecules regulate natural killer (NK) cell responses to eliminate infected and transformed cells while maintaining tolerance to healthy cells. Unlinked polymorphic gene families encode KIR receptors and HLA class I ligands and their independent segregation results in a variable number and type of iKIR + HLA pairs inherited in individuals. The diversity in the co-inheritance of iKIR + HLA pairs and activating KIR (aKIR) genes in 759 unrelated individuals from four ethnic populations was analyzed. Every individual studied inherited a minimum of one iKIR + HLA pair; suggesting that major histocompatibility complex class I-dependent inhibitory KIR signaling is essential for human NK cell function. In contrast, 13.4% of the study group lacked all aKIR genes. Twenty percent of the study group carried only one of the four iKIR + HLA pairs. Interestingly, 3% of the study group carrying only KIR2DL3 + HLA-C1 as an iKIR + HLA pair lacked aKIR genes. These data suggest that a single iKIR can constitute the minimal KIR repertoire for human NK cells. Genotypes carrying an equal number of iKIR + HLA pairs and aKIR genes represented 20% of the study group. The remaining individuals had either a dominant inhibitory KIR genotype (iKIR + HLA > aKIR) or a dominant activating KIR genotype (iKIR + HLA < aKIR). Genotypes encoding these imbalanced inhibitory and activating interactions may contribute to susceptibility or resistance to human diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Epitope Mapping
  • Ethnic Groups / genetics
  • Genotype
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Killer Cells, Natural / immunology*
  • Ligands
  • Polymorphism, Genetic
  • Receptors, Immunologic / genetics*
  • Receptors, Immunologic / metabolism*
  • Receptors, KIR
  • Receptors, KIR2DL3
  • Sequence Deletion

Substances

  • Histocompatibility Antigens Class I
  • KIR2DL3 protein, human
  • Ligands
  • Receptors, Immunologic
  • Receptors, KIR
  • Receptors, KIR2DL3