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

Dalla Chiesa, Marta and Martensen, Pia M. and Simmons, Cameron and Porakishvili, Nino and Justesen, Just and Dougan, Gordon and Roitt, Ivan 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 1365-2567

Full text is not in this repository.

Official URL: http://www3.interscience.wiley.com/journal/1189703...

This item is available in the Library Catalogue

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
Research Areas:School of Science and Technology > Natural Sciences
ID Code:3968
Useful Links:
Deposited On:12 Feb 2010 09:42
Last Modified:06 Feb 2013 11:45

Repository staff only: item control page

Full text downloads (NB count will be zero if no full text documents are attached to the record)

Downloads per month over the past year