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

Nature. 1993 Nov 4;366(6450):76-9. doi: 10.1038/366076a0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept
  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal
  • Antigens, CD*
  • Antigens, Differentiation / metabolism*
  • B7-1 Antigen / metabolism
  • B7-2 Antigen
  • Base Sequence
  • CD28 Antigens / metabolism*
  • CTLA-4 Antigen
  • Cloning, Molecular
  • DNA, Complementary
  • Humans
  • Immunoconjugates*
  • Ligands
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Tumor Cells, Cultured


  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation
  • B7-1 Antigen
  • B7-2 Antigen
  • CD28 Antigens
  • CD86 protein, human
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Cd86 protein, mouse
  • Ctla4 protein, mouse
  • DNA, Complementary
  • Immunoconjugates
  • Ligands
  • Membrane Glycoproteins
  • Recombinant Fusion Proteins
  • Abatacept