CTLA-4 is a second receptor for the B cell activation antigen B7

J Exp Med. 1991 Sep 1;174(3):561-9. doi: 10.1084/jem.174.3.561.


Functional interactions between T and B lymphocytes are necessary for optimal activation of an immune response. Recently, the T lymphocyte receptor CD28 was shown to bind the B7 counter-receptor on activated B lymphocytes, and subsequently to costimulate interleukin 2 production and T cell proliferation. CTLA-4 is a predicted membrane receptor from cytotoxic T cells that is homologous to CD28 and whose gene maps to the same chromosomal band as the gene for CD28. It is not known, however, if CD28 and CTLA-4 also share functional properties. To investigate functional properties of CTLA-4, we have produced a soluble genetic fusion between the extracellular domain of CTLA-4 and an immunoglobulin C gamma chain. Here, we show that the fusion protein encoded by this construct, CTLA4Ig, bound specifically to B7-transfected Chinese hamster ovary cells and to lymphoblastoid cells. CTLA4Ig also immunoprecipitated B7 from cell surface 125I-labeled extracts of these cells. The avidity of 125I-labeled B7Ig fusion protein for immobilized CTLA4Ig was estimated (Kd approximately 12 nM). Finally, we show that CTLA4Ig was a potent inhibitor of in vitro immune responses dependent upon cellular interactions between T and B lymphocytes. These findings provide direct evidence that, like its structural homologue CD28, CTLA-4 is able to bind the B7 counter-receptor on activated B cells. Lymphocyte interactions involving the B7 counter-receptor are functionally important for alloantigen responses in vitro.

MeSH terms

  • Abatacept
  • Amino Acid Sequence
  • Animals
  • Antigens, CD
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / immunology*
  • Antigens, Surface / metabolism*
  • B-Lymphocytes / immunology*
  • B7-1 Antigen
  • Base Sequence
  • CTLA-4 Antigen
  • Cell Line
  • Immunoconjugates*
  • In Vitro Techniques
  • Ligands
  • Lymphocyte Activation*
  • Lymphocyte Cooperation
  • Molecular Sequence Data
  • Oligonucleotides / chemistry
  • Precipitin Tests
  • Receptors, Immunologic*
  • Recombinant Fusion Proteins
  • T-Lymphocytes / immunology*


  • Antigens, CD
  • Antigens, Differentiation
  • Antigens, Surface
  • B7-1 Antigen
  • CTLA-4 Antigen
  • Immunoconjugates
  • Ligands
  • Oligonucleotides
  • Receptors, Immunologic
  • Recombinant Fusion Proteins
  • Abatacept