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.
Tahara-Hanaoka
Satoko
S
Laboratory for Immune Receptor, RIKEN Research Center for Allergy and Immunology, Tsukuba, Ibaraki 305-0074, Japan.
Shibuya
Kazuko
K
Onoda
Yuko
Y
Zhang
Hua
H
Yamazaki
Satoshi
S
Miyamoto
Akitomo
A
Honda
Shin-Ichiro
S
Lanier
Lewis L
LL
Shibuya
Akira
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000494:pharmacology / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001667:Binding, Competitive / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D005434:Flow Cytometry; D015723:Gene Library; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D000075983:Nectins; D011485:Protein Binding / Q000187:drug effects; D011991:Receptors, Virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020349:Surface Plasmon Resonance; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014170:Transformation, Genetic; D000098862:T Lineage-Specific Activation Antigen 1
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; C480027:ICAM-2 protein, mouse; D007074:Immunoglobulin G; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D008565:Membrane Proteins; D000075983:Nectins; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; C066100:poliovirus receptor; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate