Structural Basis of the Cross-reactivity of Genetically Related Human Anti-HIV-1 MAbs: Implications for Design of V3-based Immunogens

Overview

Journal Structure

Publisher Cell Press

Specialties Biochemistry
Biotechnology
Cell Biology
Molecular Biology

Date 2009 Nov 17

PMID 19913488

Citations 55

Authors

Valicia Burke

Constance Williams

Madhav Sukumaran

Seung-Sup Kim

Huiguang Li

Xiao-Hong Wang

Miroslaw K Gorny

Susan Zolla-Pazner

Xiang-Peng Kong

Affiliations

Soon will be listed here.

Abstract

Human monoclonal antibodies 447-52D and 537-10D, both coded by the VH3 gene and specific for the third variable region (V3) of the HIV-1 gp120, were found to share antigen-binding structural elements including an elongated CDR H3 forming main-chain interactions with the N terminus of the V3 crown. However, water-mediated hydrogen bonds and a unique cation-pi sandwich stacking allow 447-52D to be broadly reactive with V3 containing both the GPGR and GPGQ crown motifs, while the deeper binding pocket and a buried Glu in the binding site of 537-10D limit its reactivity to only V3 containing the GPGR motif. Our results suggest that the design of immunogens for anti-V3 antibodies should avoid the Arg at the V3 crown, as GPGR-containing epitopes appear to select for B cells making antibodies of narrower specificity than V3 that carry Gln at this position.

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