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International Immunology, Vol. 11, No. 1, 29-35, January 1999
© 1999 Japanese Society for Immunology

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

Massimo Vitale1, Roberta Castriconi4, Silvia Parolini2, Daniela Pende1, Mei-Ling Hsu3, Lorenzo Moretta1,4, David Cosman3 and Alessandro Moretta4

1 Istituto Nazionale per la Ricerca sul Cancro e Centro Biotecnologie Avanzate, 16132 Genova, Italy
2 Dipartimento di Scienze Biomediche e Biotecnologie, Università di Brescia, Brescia, Italy
3 Immunex Corp., Seattle, WA 98101, USA
4 Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, 16132 Genova, Italy

Correspondence to: L. Moretta, Laboratorio di Immunopatologia, Centro Biotecnologie Avanzate, L. go Rosanna Benzi 10, 16132 Genova, Italy

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.

Keywords: cytotoxicity, HLA class I, inhibitory receptors, NK cell

Transmitting editor: G. Doria


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