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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/19365
Title: Murine monoclonal antibodies neutralizing the cytotoxic activity of diphtheria toxin
Authors: Kanchana Usuwanthim
Anek Pootong
Urai Chaisri
Pongsri Tongtawe
Pramuan Tapchaisri
Manas Chongsa-Nguan
Wanpen Chaicumpa
Thammasat University
Mahidol University
Keywords: Immunology and Microbiology;Medicine
Issue Date: 1-Mar-2008
Citation: Asian Pacific Journal of Allergy and Immunology. Vol.26, No.1 (2008), 47-55
Abstract: In this study, murine monoclonal antibodies that specifically bound to the A and B subunits of diphtheria toxin (DT) were produced by conventional hybridoma technology using the spleens of BALB/c mice immunized with diphtheria DTP vaccine and CRM197. Monoclonal antibodies specific to the A subunit, i.e. clone AC5, as well as those specific to the B subunit, i.e. clone BB7, could neutralize the DT-mediated cytotoxicity to Vero cells in microcultures. The DT neutralizing mechanisms have yet to be determined. The MAbBB7 is hypothesized to either interfere with the DT receptor binding or with the pore forming function of the T domain of the B subunit. The MAbAC5 could neutralize the DT mediated cytotoxicity when mixed with the DT before adding to the Vero cell culture thus suggesting that the antibody interfered with the translocation of the A subunit. The A subunit-antibody complex might be too large to pass through the membrane channel formed by the T domain and thus prevent the accessibility of the A subunit to the cytosolic target. It is also possible that the MAb AC5 blocked the enzymatic active site of the enzyme catalytic subunit. While further experiments are needed to localize the epitopes of the two MAbs on-the holo-DT in order to reveal the DT neutralizing mechanisms, both MAbs in their humanized forms have a high potential as human therapeutic antibodies for diphtheria.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=45349099668&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/19365
ISSN: 0125877X
Appears in Collections:Scopus 2006-2010

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