Previous studies have demonstrated that an MHC class II molecule with an antigenic peptide genetically fused to its β-chain is capable of presenting this peptide to CD4+ T cells. We hypothesized that covalent peptide/class II complex may direct the accessory molecules to exert their function specifically onto T cells in a TCR-guided fashion. To test this hypothesis, we generated several recombinant adenoviruses expressing covalent myelin basic protein peptide/I-Au complex (MBP1-11/I-Au) and the costimulatory molecule B7-1. Functional studies demonstrated that adenovirus-infected cells are capable of activating an MBP1-11-specific T cell hybridoma. Coexpression of the B7-1 molecule and MBP1-11/I-Au by the same adenovirus leads to synergy in T cell activation elicited by virus-infected cells. Furthermore, studies in syngeneic mice infected with the various adenoviruses revealed that MBP1-11-specific T cells are specifically activated by the coexpression of B7-1 and MBP1-11/I-Au in vivo. In conclusion, the coexpression of the covalent peptide/class II complex and accessory molecules by the same adenovirus provides a unique strategy to modulate the epitope-specific T cell response in a TCR-guided fashion. This approach may be applicable to investigate the roles of other accessory molecules in the engagement of the TCR class II molecule by substituting B7-1 with other accessory molecules in the recombinant adenovirus.
ASJC Scopus subject areas
- Immunology and Allergy