The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/3/787/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 5, March 1, 1999 787-796

Articles

NKp44, A Triggering Receptor Involved in Tumor Cell Lysis by Activated Human Natural Killer Cells, Is a Novel Member of the Immunoglobulin Superfamily

Claudia Cantoni*,{ddagger}, Cristina Bottino*, Massimo Vitale*, Anna Pessino*,{ddagger}, Raffaella Augugliaro*,{ddagger}, Angela Malaspina*, Silvia Parolini§, Lorenzo Moretta*,{ddagger}, Alessandro Moretta{ddagger}, and Roberto Biassoni*

From the * Istituto Nazionale per la Ricerca sul Cancro and Centro Biotecnologie Avanzate, 16132 Genova, Italy; {ddagger} Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, 16132 Genova, Italy; and § Dipartimento di Scienze Biomediche e Biotecnologie, Università di Brescia, 25100 Brescia, Italy

Surface receptors involved in natural killer (NK) cell triggering during the process of tumor cell lysis have recently been identified. Of these receptors, NKp44 is selectively expressed by IL-2– activated NK cells and may contribute to the increased efficiency of activated NK cells to mediate tumor cell lysis. Here we describe the molecular cloning of NKp44. Analysis of the cloned cDNA indicated that NKp44 is a novel transmembrane glycoprotein belonging to the Immunoglobulin superfamily characterized by a single extracellular V-type domain. The charged amino acid lysine in the transmembrane region may be involved in the association of NKp44 with the signal transducing molecule killer activating receptor–associated polypeptide (KARAP)/DAP12. These molecules were found to be crucial for the surface expression of NKp44. In agreement with data of NKp44 surface expression, the NKp44 transcripts were strictly confined to activated NK cells and to a minor subset of TCR-{gamma}/{delta}+ T lymphocytes. Unlike genes coding for other receptors involved in NK cell triggering or inhibition, the NKp44 gene is on human chromosome 6.

Key Words: natural killer cells • activating receptor • natural cytotoxicity • immunoglobulin superfamily • cDNA

Address correspondence to Lorenzo Moretta, Laboratorio di Immunopatologia, Centro Biotecnologie Avanzate, L.go R. Benzi 10, 16132 Genova, Italy. Phone: 39-10-5737217/9; Fax: 39-10-354123; E-mail: moretta{at}sirio.cba.unige.it

1 Abbreviations used in this paper: ITAM, immunoreceptor tyrosine-based activating motif; ITIM, immunoreceptor tyrosine-based inhibitory motif; KARAP, killer activating receptor–associated polypeptide; KIR, killer inhibitory receptor; ORF, open reading frame; RT-PCR, reverse transcriptase-polymerase chain reaction; SF, superfamily.


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