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PMID: 9730896 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Molecular cloning of NKp46: a novel member of the immunoglobulin superfamily involved in triggering of natural cytotoxicity.

The Journal of experimental medicine ·Vol. 188 ·No. 5 ·1998-09-07 ·Pages 953-60

Pessino A, Sivori S, Bottino C, Malaspina A, Morelli L, Moretta L, Biassoni R, Moretta A

Abstract

NKp46 has been shown to represent a novel, natural killer (NK) cell-specific surface molecule, involved in human NK cell activation. In this study, we further analyzed the role of NKp46 in natural cytotoxicity against different tumor target cells. We provide direct evidence that NKp46 represents a major activating receptor involved in the recognition and lysis of both human and murine tumor cells. Although NKp46 may cooperate with other activating receptors (including the recently identified NKp44 molecule) in the induction of NK-mediated lysis of human tumor cells, it may represent the only human NK receptor involved in recognition of murine target cells. Molecular cloning of the cDNA encoding the NKp46 molecule revealed a novel member of the immunoglobulin (Ig) superfamily, characterized by two C2-type Ig-like domains in the extracellular portion. The transmembrane region contains the positively charged amino acid Arg, which is possibly involved in stabilizing the association with CD3zeta chain. The cytoplasmic portion, spanning 30 amino acids, does not contain immunoreceptor tyrosine-based activating motifs. Analysis of a panel of human/hamster somatic cell hybrids revealed segregation of the NKp46 gene on human chromosome 19. Assessment of the NKp46 mRNA expression in different tissues and cell types unambiguously confirmed the strict NK cell specificity of the NKp46 molecule. Remarkably, in line with the ability of NKp46 to recognize ligand(s) on murine target cells, the cDNA encoding NKp46 was found to be homologous to a cDNA expressed in murine spleen. In conclusion, this study reports the first characterization of the molecular structure of a NK-specific receptor involved in the mechanism of NK cell activation during natural cytotoxicity.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Blotting, Southern Cattle Cell Line Chromosome Mapping Cloning, Molecular Cytotoxicity, Immunologic/genetics DNA, Complementary/isolation & purification Dogs Humans Immunoglobulins/genetics Killer Cells, Natural/immunology Mice Mice, Inbred BALB C Mice, Inbred C57BL Molecular Sequence Data Multigene Family/immunology Natural Cytotoxicity Triggering Receptor 1 Organ Specificity/genetics Rabbits Rats Receptors, Immunologic/genetics,isolation & purification,physiology Transcription, Genetic/immunology Tumor Cells, Cultured
Chemicals
DNA, Complementary Immunoglobulins NCR1 protein, human Natural Cytotoxicity Triggering Receptor 1 Receptors, Immunologic
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Pessino A
Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Italy.
Sivori S
Bottino C
Malaspina A
Morelli L
Moretta L
Biassoni R
Moretta A
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.188.5.953
Published
1998-09-07
Pages
953-60
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC3207313
Subset
IM
Databases
GENBANK
AJ001383, AJ006121, AJ006122, AJ006123
External Links
PubMed source DOI: 10.1084/jem.188.5.953 PMC Full Text View journal details
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