JCM Accepts, published online ahead of print on 3 July 2007

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J. Clin. Microbiol. doi:10.1128/JCM.00508-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The amino acid residues PC^R/_KT at the positions 120 - 123 are crucial for the antigenicity of hepatitis B surface antigen

Yongjun Tian, Yang Xu, Zhenhua Zhang, Zhongji Meng, Li Qin, Mengji Lu^*, and Dongliang Yang

Division of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China; Institute of Virology, University Hospital of Essen, Essen, Germany; Department of Microbiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China

^* To whom correspondence should be addressed. Email: mengji.lu{at}uni-due.de.

The major hydrophilic region (MHR) of hepatitis B surface antigen (HBsAg) harbors conformational B cell epitopes and is the major target of neutralizing antibodies to HBsAg (anti-HBs). Mutant HBsAg (mtHBsAg) with amino acid (aa) substitutions like G145R are known to affect the binding of specific anti-HBs antibodies and their detection by conventional diagnostic assays. In the present study, we focused on the role of the aa positions 120-123 around the MHR 2 according to the spectrum of recently identified, naturally-occurring mtHBsAg. Strikingly, the aa substitutions K122I abolished the reactivity of HBsAg in all immunoassays tested so far. In comparison, the mtHBsAg G145R could be clearly detected with 4 different ELISAs based on monoclonal anti-HBs antibodies (MAbs) with high affinity. Positive immunofluorescence staining of mtHBsAg K122I was only achieved by polyclonal anti-HBs while all MAbs tested so far failed. The mtHBsAg T123N showed a low reactivity in immunoassays and appeared to be secretion defective. The aa substitution P120T reduced the binding of anti-HBs but did not completely prevent the detection of mutated HBsAg by anti-HBs MAbs. The testing of naturally occurring mtHBsAg confirmed that the presence of aa substitutions within the region 120 to 123 is strongly associated with impaired detection in immunoassays. In conclusion, the MHR 2 is essential for the HBsAg antigenicity, a fact that has not been recognized up to now.