CD80 dimensions are important for T cell co-stimulation (P1396)

Abstract Successful T cell activation depends on the recognition of antigenic peptides by the T cell receptor (TCR) together with additional signals from co-stimulatory receptors such as CD28. To determine the requirement of matching TCR and CD28 ligand complexes in optimal co-stimulation, the length of CD80 was elongated by insertion of 2 or 4 immunoglobulin domains. Despite similar binding to soluble CD28 molecules, elongated CD80 molecules were much less effective at mediating co-stimulation to primary T cells. By splitting the TCR and CD28 ligands into 2 separate APCs, the trans-costimulation assay subsequently suggests that elongated CD80s are incapable of transducing co-stimulation signals into the T cell. In addition, confocal studies using CD80-GFP fusion protein indicated that large phosphatases such as CD45 co-localised with elongated CD80 in the T cell-APC interface. Together, these results demonstrated the importance of ligand dimensions in optimal T cell co-stimulation.