Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / pharmacology
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Antigens, CD / immunology
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Antigens, CD / pharmacology
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Antigens, CD / physiology
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Antigens, Differentiation, T-Lymphocyte / genetics
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Antigens, Differentiation, T-Lymphocyte / immunology
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Antigens, Differentiation, T-Lymphocyte / metabolism*
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Binding, Competitive / drug effects
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Cell Adhesion Molecules / genetics
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Cell Adhesion Molecules / immunology
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Cell Adhesion Molecules / pharmacology
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Cell Adhesion Molecules / physiology*
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Cell Line, Tumor
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Cloning, Molecular
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Cytotoxicity, Immunologic / drug effects
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Cytotoxicity, Immunologic / immunology
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DNA, Complementary / genetics
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DNA, Complementary / isolation & purification
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Flow Cytometry
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Gene Library
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Humans
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Immunoglobulin G / genetics
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Interferon-gamma / metabolism
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Interleukin-2 / pharmacology
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Killer Cells, Natural / drug effects
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Killer Cells, Natural / immunology
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Killer Cells, Natural / metabolism
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Lymphocyte Function-Associated Antigen-1 / genetics
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Lymphocyte Function-Associated Antigen-1 / immunology
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Lymphocyte Function-Associated Antigen-1 / physiology
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Membrane Proteins / genetics
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Membrane Proteins / immunology
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Membrane Proteins / metabolism*
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Mice
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Nectins
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Protein Binding / drug effects
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Receptors, Virus / genetics
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Receptors, Virus / immunology
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Receptors, Virus / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Surface Plasmon Resonance
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T-Lymphocytes, Cytotoxic / drug effects
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T-Lymphocytes, Cytotoxic / immunology
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T-Lymphocytes, Cytotoxic / metabolism
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Tetradecanoylphorbol Acetate / pharmacology
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Transformation, Genetic
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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CD226 antigen
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Cell Adhesion Molecules
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DNA, Complementary
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ICAM-2 protein, mouse
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Immunoglobulin G
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Interleukin-2
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Lymphocyte Function-Associated Antigen-1
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Membrane Proteins
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Nectins
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Receptors, Virus
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Recombinant Fusion Proteins
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poliovirus receptor
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Interferon-gamma
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Tetradecanoylphorbol Acetate