Recombinant antibodies containing an engineered B-cell epitope capable of eliciting conformation-specific antibody responses.
The immunogenicity of a soluble, non-self protein or peptide can be greatly enhanced by injecting this antigen coupled to an antibody specific for class II MHC molecules in the recipient. This adjuvant-independent immunization strategy is known as immunotargeting. We have investigated the ability of a mouse anti-class II MHC antibody to provide the three-dimensional framework for the reconstitution of a heterologous conformational B-cell epitope, specifically the A loop epitope from the influenza virus hemagglutinin (HA). From a panel of three anti-class II MHC immunoglobulin (Ig)-A loop constructs, we found that one of these, an insertion into the FR3 region of the Ig molecule, retained its specificity for mouse I-Ak. Although mouse monoclonal antibodies specific for the A loop region in the HA molecule were unable to react with the Ig-A loop variants, we did find that the heavy chain CDR3 insertion construct was able to elicit an A loop-specific, HA-reactive antibody response when used as an immunogen in rabbits. These results demonstrate the potential for the Ig molecule to function successfully as a structural framework for the reconstitution and presentation of heterologous conformational B-cell epitopes.
Cook
J
J
Department of Immunology, University of Toronto, Ontario, Canada.
Barber
B H
BH
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000917:Antibody Formation; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D001402:B-Lymphocytes / Q000276:immunology*; D000939:Epitopes; D005260:Female; D005818:Genetic Engineering; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007070:Immunoglobulin A / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011994:Recombinant Proteins