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Salivary gland epithelial cells (SGEC) express a novel alternate transcript of the B7.2 costimulatory molecule that lacks the CD28/CTLA4-binding IgV-like domain
Arthritis Res Ther volume 6, Article number: 99 (2004)
Epithelial cells appear to have a central role in the pathogenesis of Sjögren's syndrome (SS), by acting as antigen-presenting cells. SGEC lines established from minor SG biopsies of SS patients express MHC and B7 costimulatory molecules. We previously showed that B7.2 molecules expressed by SGEC display distinctive binding properties denoted by the functional interaction with CD28 receptor and reduced binding to the negative immune regulator CTLA4.
Objective and Methods
To delineate the role of RNA modifications in the SGEC–B7.2 protein binding properties, we applied a RT-PCR protocol that amplifies the entire coding region of the B7.2 mRNA. The amplified PCR products were sequenced and characterized.
SGEC were found to express three distinct alternate transcripts of the B7.2 molecule. These included the two previously described transcripts (encoding the full-length and the soluble form, respectively), as well as a third novel form (designated as B7.2C). B7.2C is characterized by exon 4 deletion, which encodes the IgV-like binding domain of the B7.2 protein to the CD28 and CTLA4 receptors. The conservation of the signaling peptide and the transmembrane region in the B7.2C transcript suggests the membranous expression of the encoded protein. The cell surface expression of the B7.2C protein was verified in CHO cell lines transfected with this transcript. B7.2C mRNA analysis of peripheral blood cell subpopulations (monocytes, T and B cells) revealed exclusive expression by monocytes.
The role of B7.2C transcript remains to be determined. The clustering of B7.2 molecules and the development of a network has been considered necessary for their effective interaction with CD28/CTLA4 receptors. Thus, the co-expression of the full length B7.2 with the truncated B7.2C protein (that lacks the CD28/CTLA4-binding sites) may lead to negative regulation of T cell activation by interference of B7.2C in the formation of B7.2 clusters.
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Kapsogeorgou, E., Moutsopoulos, H. & Manoussakis, M. Salivary gland epithelial cells (SGEC) express a novel alternate transcript of the B7.2 costimulatory molecule that lacks the CD28/CTLA4-binding IgV-like domain. Arthritis Res Ther 6, 99 (2004). https://doi.org/10.1186/ar1141
- Costimulatory Molecule
- Alternate Transcript
- Entire Code Region
- Exclusive Expression
- Salivary Gland Epithelial Cell