The leukocyte Ig-like receptor (LIR)-1 for the cytomegalovirus UL18 protein displays a broad specificity for different HLA class I alleles: analysis of LIR-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-18 protein. In this study, we have analyzed the expression and function of LIR-1 in human NK cells. We show that LIR-1 is expressed by a subset of NK cells variable in size among different donors. When compared to the known HLA class I-specific NK receptors, the expression of LIR-1 was found to be partially overlapped with that of CD94-NKG2A or with that of killer inhibitory receptors (KIR) belonging to the Ig superfamily. The use of the soluble form of UL-18 molecule revealed, in double fluorescence analysis, a selective binding to LIR-1 + cells while no correlation was observed between expression of either KIR or CD94-NKG2A molecules and ability to bind UL18. We further determined whether LIR-1 could also function as receptor for HLA class 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.
Vitale
M
M
Istituto Nazionale per la Ricerca sul Cancro e Centro Biotecnologie Avanzate, Genova, Italy.
Castriconi
R
R
Parolini
S
S
Pende
D
D
Hsu
M L
ML
Moretta
L
L
Cosman
D
D
Moretta
A
A
D000483:Alleles; D015703:Antigens, CD / Q000276:immunology; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D037181:Lectins, C-Type; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008562:Membrane Glycoproteins / Q000276:immunology; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000276:immunology*; D054340:Receptors, KIR; D012995:Solubility; D014764:Viral Proteins / Q000276:immunology*
D015703:Antigens, CD; D015395:Histocompatibility Antigens Class I; C497869:KLRD1 protein, human; C105299:LILRB1 protein, human; D037181:Lectins, C-Type; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008562:Membrane Glycoproteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D014764:Viral Proteins