title: B70 antigen is a second ligand for CTLA-4 and CD28.
abstract: The membrane antigen B7/BB1 (refs 1, 2) is expressed on activated B cells, macrophages and dendritic cells, and binds to a counter-receptor, CD28, expressed on T lymphocytes and thymocytes. Interaction between CD28 and B7 results in potent costimulation of T-cell activation initiated through the CD3/T-cell receptor complex. Discrepancies between results with anti-CD28 and anti-B7 antibodies have suggested the existence of a second ligand for CD28 and CTLA-4 (refs 3, 6-8). We have generated a monoclonal antibody, IT2, that reacts with a 70K glycoprotein (B70). B70 complementary DNA was cloned from a B-lymphoblastoid cell line library and encodes a new protein of the immunoglobulin superfamily with limited homology to B7. B70 is expressed on resting monocytes and dendritic cells and on activated, but not resting, T, NK and B lymphocytes. IT2 substantially inhibited the binding of a CTLA4-immunoglobulin fusion protein to human B-lymphoblastoid cell lines and, together with anti-B7 antibody, completely blocked CTLA-4 binding. Further IT2 efficiently inhibited primary allogeneic mixed lymphocyte responses. These findings indicate that B70 is a second ligand for CD28 and CTLA-4 and may play an important role for costimulation of T cells in a primary immune response.
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Azuma
authors.forename: D
authors.initials: D
authors.lastname: Ito
authors.forename: H
authors.initials: H
authors.lastname: Yagita
authors.forename: K
authors.initials: K
authors.lastname: Okumura
authors.forename: J H
authors.initials: JH
authors.lastname: Phillips
authors.forename: L L
authors.initials: LL
authors.lastname: Lanier
authors.forename: C
authors.initials: C
authors.lastname: Somoza
mesh_terms: D000069594:Abatacept; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D001483:Base Sequence; D018106:CD28 Antigens / Q000378:metabolism*; D060908:CTLA-4 Antigen; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006801:Humans; D018796:Immunoconjugates; D008024:Ligands; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D018076:DNA, Complementary; D018796:Immunoconjugates; D008024:Ligands; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D000069594:Abatacept