The leukocyte Ig-like receptor (LIR)-1 for the cytomegalovirus UL18 protein displays a broad specificity for different HLA class I alleles: analysis of LID-1(+) NK cell clones

Leukocyte Ig-like receptor (LIR)-1 is a member of the Ig superfamily which has been shown to bind the human cytomegalovirus MHC class I homologue UL-1 8 protein. In this study, we have analyzed the expression and function of L IR-1 in human NK cells, We show that LIR-1 is expressed by a subset of NK c ells variable in size among different donors. When compared to the known HL A class I-specific NK receptors, the expression of LIR-1 was found to be pa rtially overlapped with that of CD94-NKG2A or with that of killer inhibitor y receptors (KIR) belonging to the Ig superfamily. The use of the soluble f orm of UL-18 molecule revealed, in double fluorescence analysis, a selectiv e binding to LIR-1(+) cells while no correlation was observed between expre ssion of either KIR or CD94-NKG2A molecules and ability to bind UL18. We fu rther determined whether LIR-1 could also function as receptor for HLA clas s I molecules. To this end, we assessed the capability of LIR-1(+) NK cell clones of lysing HLA class I- target cells transfected with different class I alleles, including HLA-A, -B, -C and -G alleles, Data revealed that LIR- 1 functions as a broad HLA class I-specific inhibitory receptor recognizing different alleles coded for by different HLA loci.