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Refocusing of B-cell responses following a single amino acid substitution in an antigen

Dalla Chiesa, Marta and Martensen, Pia and Simmons, Cameron and Porakishvili, Nino and Justesen, Just and Dougan, Gordon and Roitt, Ivan M. and 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 0019-2805

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Official URL: http://dx.doi.org/10.1046/j.1365-2567.2001.01242.x

Abstract

Intranasal immunization of BALB/c strain mice was carried out using baculovirus-derived human chorionic gonadotrophin (hCG) β-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 hCGβ, a mutated hCGβ-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 hCGβ 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.

Item Type:Article
Additional Information:Online ISSN 1365-2567
Research Community:University of Westminster > Life Sciences, School of
ID Code:434
Deposited On:30 Aug 2005
Last Modified:16 Dec 2009 10:53

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