| 2008 |
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| Usuwanthim, K., Pootong, A., Chaisri, U., Tongtawe, P., Tapchaisri, P., Chongsa-Nguan, M., and
Chaicumpa, W. |
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| Faculty of Allied Health Sciences, Thammasat University, Pathum-thani, Thailand |
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| 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 |
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| Published in:Asian Pac.J.Allergy Immunol. 26[1], 47-55. 2008. |
