Broadly neutralizing anti-HBV antibody binds to non-epitope regions of preS1.
Broadly neutralizing anti-hepatitis B virus (HBV) antibody HzKR127 undergoes a fairly large conformational change of CDR H3 loop upon binding to HBV preS1 epitope peptide. In this study, we identified low-affinity antibody-binding sites in the largely unstructured preS1 region by nuclear magnetic resonance and biochemical studies, indicating that the antibody binds to the preS1 region outside the major immune epitope with low affinity. Surface plasma resonance experiments showed that the full-length preS1 has approximately three fold higher affinity for HzKR127 Fab than the preS1 epitope peptide, suggesting that the presence of low-affinity sites in the preS1 region increases the antibody-binding affinity. Therefore, the low-affinity binding of the antibody to non-epitope regions of preS1 may contribute to effective neutralization.
Chi
Seung-Wook
SW
Medical Proteomics Research Center, KRIBB, Daejeon 305-806, Republic of Korea. swchi@kribb.re.kr
Kim
Jinki
J
Yi
Gwan-Su
GS
Hong
Hyo Jeong
HJ
Ryu
Seong Eon
SE
D000937:Antigen-Antibody Reactions; D001665:Binding Sites; D000939:Epitopes; D006510:Hepatitis B Antibodies / Q000378:metabolism*; D006514:Hepatitis B Surface Antigens / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D011487:Protein Conformation; D011498:Protein Precursors / Q000378:metabolism*; D020349:Surface Plasmon Resonance
D000939:Epitopes; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; C050806:presurface protein 1, hepatitis B surface antigen