Mapping the antigenic determinants and reducing the immunogenicity of trichosanthin by site-directed mutagenesis |
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Authors: | Qunxing An Sanhua Wei Shijie Mu Xianqing Zhang Yingfeng Lei Wei Zhang Ning Jia Xiaodong Cheng Ailing Fan Zhidong Li Zhikai Xu |
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Affiliation: | (1) Department of Microbiology, Fourth Medical University of PLA, Xi’an, 710032, China;(2) Department of Blood Transfusion, Xijing Hospital, Fourth Medical University of PLA, Xi’an, 710033, China;(3) Department of Clinical Laboratories, Xijing Hospital, Fourth Medical University of PLA, Xi’an, 710033, China |
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Abstract: | Summary Trichosanthin (TCS) is a type I ribosome-inactivating protein (RIP) possessing multiple pharmacological properties. One of its interesting properties is to inhibit human immunodeficiency virus (HIV) replication but its strong immunogenicity has limited the repeated clinical administration. To map the antigenic determinants and reduce the immunogenicity of TCS, two potential antigenic sites (YFF81–83 and KR173–174) were identified by computer modeling, and then three TCS mutants namely TCSYFF81–83ACS, TCSKR173–174CG, and TCSYFF-KR were constructed by site-directed mutagenesis. The RI activity and DNase-like activity of the three constructed TCS mutants were similar to natural TCS but with much lower immunogenicity. Results suggested that the two selected sites are all located at or near the antigenic determinants of TCS. In toxicity studies, the LD50 of the three TCS mutants was not different from natural TCS. These findings would be useful in designing a better therapeutic agent for AIDS.Qunxing An and Sanhua Wei equally contribute to this work. |
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Keywords: | human immunodeficiency virus immunogenicity ribosome-inactivating protein site-directed mutagenesis trichosanthin |
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