LILRB1 polymorphism and surface phenotypes of natural killer cells.

Leukocyte Ig-like receptor (LIR)-1 is an inhibitory receptor that binds a broad range of class I HLA molecules and is encoded by the LILRB1 gene within the leukocyte receptor complex. In contrast to uniform expression on monocytes and B cells, LIR-1 expression on natural killer (NK) cells varies considerably between individuals. To investigate how polymorphism is related to the observed patterns of expression, we analyzed the LILRB1 gene and its transcriptional activity in a group of individuals with various levels of expression on NK cells. We found that LILRB1 transcription is correlated with surface protein expression on NK cells. In a cohort of 24 donors, we found high expression on NK cells to be associated with three linked SNPs (AGG verses GAA) within the putative regulatory region. We also identified several new protein variants and observed variants with P, T, T, and I at positions 68, 95, 142, and 155, respectively, more frequently in donors with low expression on NK cells. These results suggest that there is a significant degree of diversity within the LILRB1 locus and that it influences expression patterns on NK cells. These genetic differences may underpin variation in individual immune responses involving LIR-1 on NK cells.