T-Cell Antigen CD28 Mediates Adhesion with B Cells by Interacting with Activation Antigen B7/BB-1

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 87; no. 13; pp. 5031 - 5035
• Main Authors: Linsley, Peter S., Clark, Edward A., Ledbetter, Jeffrey A.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 01.07.1990; National Acad Sciences
• Subjects: Animals; Antibodies, Monoclonal; Antigens; Antigens, CD - genetics; Antigens, CD - immunology; Antigens, Differentiation, B-Lymphocyte - immunology; Antigens, Differentiation, T-Lymphocyte - genetics; Antigens, Differentiation, T-Lymphocyte - immunology; B lymphocytes; B-Lymphocytes - immunology; CD28 Antigens; Cell Adhesion; Cell Line; Cell lines; CHO cells; Cloning, Molecular; Complementary DNA; COS cells; Humans; Kinetics; Ligands; Molecules; Plasmids; T lymphocytes; T-Lymphocytes - immunology; Transfection; Tumor Cells, Cultured - immunology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.87.13.5031

Studies using monoclonal antibodies (mAbs) have implicated the homodimeric glycoprotein CD28 as an important regulator of human T-cell activation, in part by posttranscriptional control of cytokine mRNA levels. Although the CD28 antigen has functional and structural characteristics of a receptor, a natural ligand for this molecule has not been identified. Here we show that the CD28 antigen, expressed in Chinese hamster ovary (CHO) cells, mediated specific inter-cellular adhesion with human lymphoblastoid and leukemic B-cell lines and with activated primary murine B cells. CD28-mediated adhesion was not dependant upon divalent cations. Several mAbs were identified that inhibited CD28-mediated adhesion, including mAb BB-1 against the B-cell activation antigen B7/BB-1 and some mAbs against major histocompatibility complex class I antigens. B7/BB-1 expression correlated closely with CD28-mediated adhesion, but class I expression did not. Transfected COS cells expressing the B7/BB-1 antigen adhered to CD28+CHO cells; this adhesion was blocked by mAbs to CD28 and B7/BB-1. The specific recognition by CD28 of the B-cell activation antigen B7/BB-1 represents a heterophilic interaction between members of the immunoglobulin superfamily that may serve to regulate T-cell cytokine levels at sites of B-cell activation.