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PHENOTYPIC DIVERSITY OF THE CONSERVED KILLER CELL LECTIN-LIKE RECEPTOR GENES.
Zeying Du Ph.D. , Elaine F. Reed Ph.D. and Raja Rajalingam Ph.D. . 1 UCLA Immunogenetics Center, Dept. of Pathology and Laboratory Medicine, Los Angeles, CA, USA .
NK cell function is regulated by structurally two distinct families of receptors: killer cell Ig-like receptors (KIR) and killer cell lectin-like receptors (KLR). The KLR receptors are encoded by a family of six genes: CD94, NKG2A, NKG2C, NKG2D, NKG2E and NKG2F. Although KLR genes are known to be conserved, a recent study in Japanese revealed that some individuals do not have activating NKG2C receptor gene. In the present study, we have observed similar frequency of NKG2C-deletion in other populations including Caucasians (n=175), Hispanics (n=109), Blacks (n=52) and Asians (n=137). Other KLR genes, including the newly defined NKG2F are ubiquitously found in all subjects we analyzed. NKG2A and NKG2C recognize the non-classical class I HLA-E, the expression of which is affected by dimorphism at amino acid position 107. Whereas the HLA-EG107 allele is readily expressed, the HLA-ER107 allele hardly reaches the cell surface. Subtyping of HLA-E on our study panel revealed that 30% are homozygotes for low-expression alleles, suggesting that one third of the human population presumably use KLR receptors sub-optimally to regulate their NK cell function. Although the KLR genes are ubiquitously present in all individuals, their expressions vary between individuals. Our real-time PCR analysis revealed that the expression of different KLR genes is stable within an individual but varies between individuals. Particularly, the activating receptor NKG2C expression varies drastically between individuals. Although the KLR genes are conserved, variation in KLR and HLA-E ligand expressions could influence the individuals
NK cell function. What controls the KLR expression? -polymorphism within KLR genes or environmental factors -- needs to be investigated.