Functional characterization of DNAM-1 (CD226) interaction with its ligands PVR (CD155) and nectin-2 (PRR-2/CD112)
Copyright policy )Functional characterization of DNAM-1 (CD226) interaction with its ligands PVR (CD155) and nectin-2 (PRR-2/CD112)
CD226 (DNAM-1) is an adhesion molecule involved in NK and T cell-mediated cytotoxicity against certain tumors. Here, we have identified the human poliovirus receptor-related (PRR) family members CD155 [poliovirus receptor (PVR)] and CD112 (nectin-2/PRR-2) as the ligands for human CD226. Ectopic expression of human CD155 and/or CD112 rendered mouse BW5147 T cells more susceptible to IL-2-activated T and NK cell-mediated cytotoxicity, and killing was specifically inhibited by anti-CD226 mAb, demonstrating functional interactions of CD226 with CD155 and CD112. Although the binding affinities between soluble CD226 and CD155 or CD112 were comparable, the homophilic interaction of cell-surface CD112 may adversely affect CD226 binding to CD112. We also demonstrate that ligation of CD226 and LFA-1 with their respective ligands cooperates in triggering cytotoxicity and cytokine secretion by T and NK cells.
- University of Tsukuba Japan
Antigens, Differentiation, T-Lymphocyte, Cytotoxicity, Immunologic, DNA, Complementary, Antibodies, Monoclonal, Membrane Proteins, Flow Cytometry, Binding, Competitive, Lymphocyte Function-Associated Antigen-1, Killer Cells, Natural, Interferon-gamma, Mice, Antigens, CD, Cell Line, Tumor, Immunoglobulin G, Animals, Humans, Interleukin-2, Cloning, Molecular, Cell Adhesion Molecules, Gene Library
Antigens, Differentiation, T-Lymphocyte, Cytotoxicity, Immunologic, DNA, Complementary, Antibodies, Monoclonal, Membrane Proteins, Flow Cytometry, Binding, Competitive, Lymphocyte Function-Associated Antigen-1, Killer Cells, Natural, Interferon-gamma, Mice, Antigens, CD, Cell Line, Tumor, Immunoglobulin G, Animals, Humans, Interleukin-2, Cloning, Molecular, Cell Adhesion Molecules, Gene Library
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