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Identification and Characterization of a Transmembrane Isoform of CD160 (CD160-TM), a Unique Activating Receptor Selectively Expressed upon Human NK Cell Activation¹

Institeut National de la Santé et de la Recherche Médicale Unite 841, Departments of Immunology, Dermatology, and Oncology, Université Paris 12, Faculté de Médecine de Créteil, Créteil, France

CD160 has been initially identified as a GPI-anchored MHC-class I activating receptor mainly expressed on peripheral blood NK cells. Herein, we report the identification of three additional CD160-related mRNAs generated through alternative splicings of the CD160 gene, among which one encoded a putative CD160 transmembrane isoform (CD160-TM). We first establish that CD160-TM surface expression is highly restricted to NK cells and is activation-dependent. Additionally, we provide evidence that CD160-TM represents a novel activating receptor, as assessed by the increased CD107a NK cell surface mobilization observed upon its engagement. Finally, we demonstrate that the CD160-TM cytoplasmic tail is by itself sufficient to mediate the recruitment of Erk1/2 signaling pathway, and that the initiation of this activation process is dependent on the Src-family kinase p56^lck. The identification of CD160-TM therefore provides new possibilities regarding the role of CD160 isoforms in the regulation of NK cell functions.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Institut National de la Santé et de la Recherche Médicale and Paris XII University.

² A.B. and A.M.-C. are co-senior authors of this work.

³ Address correspondence and reprint requests to Dr. Armand Bensussan, Institut National de la Santé et de la Recherche Médicale Unite 841 (EQ02), Faculté de Médecine de Créteil, 8 rue du Général Sarrail, 94010 Créteil Cedex, France. E-mail address: armand.bensussan{at}inserm.fr

⁴ Abbreviations used in this paper: NCR, natural cytotoxicity receptor; TM, transmembrane; PB, peripheral blood.

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