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

doi:10.1084/jem.174.3.561

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

PS Linsley, W Brady, M Urnes, LS Grosmaire, NK Damle and JA Ledbetter
Oncogen Division, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.

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.
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Subauste, C. S., Wessendarp, M., Sorensen, R. U., Leiva, L. E. (1999). CD40-CD40 Ligand Interaction Is Central to Cell-Mediated Immunity Against Toxoplasma gondii: Patients with Hyper IgM Syndrome Have a Defective Type 1 Immune Response That Can Be Restored by Soluble CD40 Ligand Trimer. J. Immunol. 162: 6690-6700 [Abstract] [Full Text]
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