Recombinant Adenovirus Coexpressing Covalent Peptide/MHC Class II Complex and B7-1: In Vitro and In Vivo Activation of Myelin Basic Protein-Specific T Cells

Abstract

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.

A Novel Murine Model of Graves’ Hyperthyroidism with Intramuscular Injection of Adenovirus Expressing the Thyrotropin Receptor

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Keratocan Expression of Murine Keratocytes Is Maintained on Amniotic Membrane by Down-regulating Transforming Growth Factor-β Signaling

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Keratocan and Lumican Regulate Neutrophil Infiltration and Corneal Clarity in Lipopolysaccharide-induced Keratitis by Direct Interaction with CXCL1

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