Recognition Properties of V3-Specific Antibodies to V3 Loop Peptides Derived from HIV-1 gp120 Presented in Multiple Conformations

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• 作者：J. G. Huisman ; A. Carotenuto ; A. F. Labrijn ; C. H. M. Papavoine ; J. D. Laman ; M. M. Schellekens ; M. H. G. M. Koppelman ; and C. W. Hilbers
• 刊名：Biochemistry
• 出版年：2000
• 出版时间：September 5, 2000
• 年：2000
• 卷：39
• 期：35
• 页码：10866 - 10876
• 全文大小：207K
• 年卷期：v.39,no.35(September 5, 2000)
• ISSN：1520-4995

文摘

To identify structural constraints and amino acid sequences important for antibody recognitionof the third variable domain (V3) of HIV-1 gp120, we have studied the solution conformation of three35-mer circular V3 loop peptides derived from HIV-1 strains which differ in syncytium- (SI) and non-syncytium-inducing (NSI) capacity. In addition to 2D NMR and CD analyses, fluid- and solid-phaseimmunoassays were performed using V3-specific antibodies to V3 peptides and gp120 derived fromdifferent strains of HIV-1. NMR and CD spectroscopy indicated that circular and linear V3 loops exist inwater as a dynamic ensemble of multiple conformations. Amino acid substitutions and biochemicalmodifications of the V3 loop were found to affect antibody binding depending on the presentation of theantigens. From NMR observations and immunological experiments, we provide evidence for a V3 loopspecific monoclonal antibody interaction which is directed predominantly against linear epitopes ratherthan against discontinuous epitopes. The absence of a single defined solution conformation of 35-mercircular V3 peptides should be taken into account when using V3-related peptides to investigate structuralelements in the V3 domain of the gp120 envelope protein of HIV-1 involved in biological processes ofthe virus.