Dalla Chiesa, Marta, Martensen, Pia, Simmons, Cameron, Porakishvili, Nino, Justesen, Just, Dougan, Gordon, Roitt, Ivan M., Delves, Peter J. and Lund, Torben (2001) Refocusing of B-cell responses following a single amino acid substitution in an antigen. Immunology, 103 (2). pp. 172-178. ISSN 0019-2805Full text not available from this repository.
Intranasal immunization of BALB/c strain mice was carried out using baculovirus-derived human chorionic gonadotrophin (hCG) ?-chain, together with Escherichia coli heat-labile enterotoxin. Gonadotrophin-reactive immunoglobulin A (IgA) was induced in a remote mucosal site, the lung, in addition to a systemic IgG response. The extensive sequence homology with luteinizing hormone (LH) results in the production of LH cross-reactive antibodies when holo-hCG is used as an immunogen. In contrast to wild-type hCG?, a mutated hCG?-chain containing an arginine to glutamic acid substitution at position 68 did not induce the production of antibodies which cross-react with LH. Furthermore, the epitopes utilized in the B-cell response to the mutated hCG? shifted away from the immunodominant region of the parent wild-type molecule towards epitopes within the normally weakly immunogenic C terminus. This shift in epitope usage was also seen following intramuscular immunization of rabbits. Thus, a single amino acid change, which does not disrupt the overall structure of the molecule, refocuses the immune response away from a disadvantageous cross-reactive epitope region and towards a normally weakly immunogenic but antigen-unique area. Similar mutational strategies for epitope-refocusing may be applicable to other vaccine candidate molecules.
|Additional Information:||Online ISSN 1365-2567|
|Subjects:||University of Westminster > Science and Technology > Life Sciences, School of (No longer in use)|
|Depositing User:||Users 4 not found.|
|Date Deposited:||30 Aug 2005|
|Last Modified:||16 Dec 2009 10:53|
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