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

• Published in: The Journal of immunology (1950) Vol. 182; no. 1; pp. 63 - 71
• Main Authors: Giustiniani, Jerome, Bensussan, Armand, Marie-Cardine, Anne
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.01.2009
• Subjects: Amino Acid Sequence; Antigens, CD - biosynthesis; Antigens, CD - genetics; Antigens, CD - isolation & purification; Antigens, CD - physiology; Base Sequence; CD8-Positive T-Lymphocytes - immunology; Cell Line; Cell Line, Tumor; Clone Cells; Gene Expression Regulation - immunology; GPI-Linked Proteins; Humans; Jurkat Cells; Killer Cells, Natural - cytology; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Membrane Proteins - biosynthesis; Membrane Proteins - genetics; Membrane Proteins - isolation & purification; Membrane Proteins - physiology; Molecular Sequence Data; Protein Isoforms - biosynthesis; Protein Isoforms - genetics; Protein Isoforms - isolation & purification; Protein Isoforms - physiology; Receptors, Immunologic - biosynthesis; Receptors, Immunologic - genetics; Receptors, Immunologic - isolation & purification; Receptors, Immunologic - physiology; Resting Phase, Cell Cycle - genetics; Resting Phase, Cell Cycle - immunology; RNA, Messenger - isolation & purification
• ISSN: 0022-1767; 1550-6606; 1550-6606
• DOI: 10.4049/jimmunol.182.1.63

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 p56lck. The identification of CD160-TM therefore provides new possibilities regarding the role of CD160 isoforms in the regulation of NK cell functions.