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.
Previous studies have demonstrated that an MHC class II molecule with an antigenic peptide genetically fused to its beta-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-A(u) complex (MBP(1-11)/I-A(u)) and the costimulatory molecule B7-1. Functional studies demonstrated that adenovirus-infected cells are capable of activating an MBP(1-11)-specific T cell hybridoma. Coexpression of the B7-1 molecule and MBP(1-11)/I-A(u) 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 MBP(1-11)-specific T cells are specifically activated by the coexpression of B7-1 and MBP(1-11)/I-A(u) 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.
Chen
J
J
Division of Rheumatology and Immunology, Tufts University School of Medicine and New England Medical Center, Boston, MA 02111, USA.
Huber
B T
BT
Grand
R J
RJ
Li
W
W
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D018122:B7-1 Antigen / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D006825:Hybridomas; D007275:Injections, Intravenous; D008213:Lymphocyte Activation / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D011995:Recombination, Genetic / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000821:virology; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
D018122:B7-1 Antigen; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D010446:Peptide Fragments; C405722:myelin basic protein 1-11