Receptor-ligand analyses define minimal killer cell Ig-like receptor (KIR) in humans.
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.
Du
Zeying
Z
UCLA Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, 1000 Veteran Avenue, Room No. 1-536, Los Angeles, CA 90095-1652, USA.
Gjertson
David W
DW
Reed
Elaine F
EF
Rajalingam
Raja
R
D018604:Epitope Mapping; D005006:Ethnicity / Q000235:genetics; D005838:Genotype; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D011110:Polymorphism, Genetic; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism*; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3; D017384:Sequence Deletion
D015395:Histocompatibility Antigens Class I; C515078:KIR2DL3 protein, human; D008024:Ligands; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3