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

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 prolifera...

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Bibliographic Details
Published in:The Journal of experimental medicine 1991-09, Vol.174 (3), p.561-569
Main Authors: LINSLEY, P. S, BRADY, W, URNES, M, GROSMAIRE, L. S, DAMLE, N. K, LEDBETTER, J. A
Format: Article
Language:English
Subjects:
Abatacept
Amino Acid Sequence
Animals
Antigens, CD
Antigens, Differentiation - genetics
Antigens, Differentiation - immunology
Antigens, Surface - metabolism
B-Lymphocytes - immunology
B7-1 Antigen
Base Sequence
Biological and medical sciences
Cell Line
CTLA-4 Antigen
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Immunobiology
Immunoconjugates
In Vitro Techniques
Ligands
Lymphocyte Activation
Lymphocyte Cooperation
Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation
Molecular Sequence Data
Oligonucleotides - chemistry
Precipitin Tests
Receptors, Immunologic
Recombinant Fusion Proteins
T-Lymphocytes - immunology
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Summary: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.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.174.3.561