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

被引:113
作者
Du, Zeying [1 ]
Gjertson, David W. [1 ]
Reed, Elaine F. [1 ]
Rajalingam, Raja [1 ]
机构
[1] Univ Calif Los Angeles, Dept Pathol & Lab Med, David Geffen Sch Med, Los Angeles, CA 90095 USA
关键词
natural killer cells; MHC; tolerance; human; gene regulation; IMMUNOGLOBULIN-LIKE RECEPTOR; HUMAN NATURAL-KILLER; MHC-CLASS-I; HLA-B MOLECULES; ETHNIC-GROUPS; INHIBITORY RECEPTOR; GENE-CONTENT; NK CELLS; AMINO-ACID; HEMATOPOIETIC TRANSPLANTS;
D O I
10.1007/s00251-006-0168-4
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
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页码:1 / 15
页数:15
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