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B70 antigen is a second ligand for CTLA-4 and CD28

Naturevolume 366pages7679 (1993) | Download Citation

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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 thymocytes3. Interaction between CD28 and B7 results in potent costimulation of T-cell activation initiated through the CD3/T-cell receptor complex4,5. 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.

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Affiliations

  1. Department of Immunology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113, Japan

    • Miyuki Azuma
    • , Daisuke Ito
    • , Hideo Yagita
    •  & Ko Okumura
  2. Department of Oral and Maxillo-facial Surgery, Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113, Japan

    • Daisuke Ito
  3. Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, 901 California Avenue, Palo Alto, California, 94304, USA

    • Joseph H. Phillips
    • , Lewis L. Lanier
    •  & Chamorro Somoza

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https://doi.org/10.1038/366076a0

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