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Laboratory of Cellular and Molecular Immunology, Department of Pathophysiology, School of Medicine, National University of Athens, Athens, Greece
B7-2 (CD86) costimulatory molecules are pivotal for the regulation of T cell responses. In this study, a novel human B7-2 alternate transcript (termed B7-2C) is described. This transcript is characterized by the deletion of exon 4 that encodes the IgV-like counter-receptor binding domain of the B7-2 protein (full-length; B7-2A). B7-2C was detected as mRNA and cell surface protein in human non-neoplastic salivary gland epithelial cells and monocytes, but not in fibroblasts, T cells, B cells, dendritic cells, and several epithelial tumor cell lines. In monocytes, B7-2C protein expression was found to be significantly down-regulated following activation. The analysis of Chinese hamster ovary (CHO) single-transfected (CHO-B7-2C) and double-transfected (CHO-B7-2A/B7-2C) cell lines had indicated that cell surface B7-2C expression is by itself unable to provide T cell costimulation, but inhibits the transmission of costimulatory signals via B7-2A (by 23–69%). Such inhibition was found to depend on the relative cell surface expression of B7-2A and B7-2C proteins, as it occurred in CHO-B7-2A/B7-2C transfectants with significantly lower B7-2A to B7-2C ratios (1.0–3.5), compared with those with unaffected B7-2A-mediated costimulatory function (10.0–19.5). Our findings suggest that B7-2C is expressed by monocytes, as well as by nonimmune cells with potential Ag-presenting capacity (such as salivary gland epithelial cells). The expression of B7-2C on certain B7-2A-expressing cells appears to represent a mechanism for the fine tuning of B7-2A-mediated costimulatory signals, possibly through the interruption of B7-2A clustering required for the productive interaction between B7-2A and cognate receptors.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the Hellenic Secretariat for Research and Technology, the Lilian Voudouri Foundation, and the Hellenic Association of Autoimmune Diseases Patients (to E.K.K.).
2 Address correspondence and reprint requests to Dr. Menelaos N. Manoussakis, Department of Pathophysiology, School of Medicine, National University of Athens, 75 Mikras Asias Street, Athens 115 27, Greece. E-mail address: menman{at}med.uoa.gr
3 Abbreviations used in this paper: SGEC, salivary gland epithelial cell; CHO, Chinese hamster ovary; PGN, peptidoglycan; DC, dendritic cell.
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