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Crystal Structure of a Neutralizing Human IgG Against HIV-1: A Template for Vaccine Design

2001; American Association for the Advancement of Science; Volume: 293; Issue: 5532 Linguagem: Inglês

10.1126/science.1061692

1095-9203

Erica Ollmann Saphire, Paul W.H.I. Parren, Ralph Pantophlet, Michael B. Zwick, Garrett M. Morris, Pauline M. Rudd, Raymond A. Dwek, Robyn L. Stanfield, Dennis R. Burton, Ian A. Wilson,

Immune Cell Function and Interaction

We present the crystal structure at 2.7 angstrom resolution of the human antibody IgG1 b12. Antibody b12 recognizes the CD4-binding site of human immunodeficiency virus–1 (HIV-1) gp120 and is one of only two known antibodies against gp120 capable of broad and potent neutralization of primary HIV-1 isolates. A key feature of the antibody-combining site is the protruding, finger-like long CDR H3 that can penetrate the recessed CD4-binding site of gp120. A docking model of b12 and gp120 reveals severe structural constraints that explain the extraordinary challenge in eliciting effective neutralizing antibodies similar to b12. The structure, together with mutagenesis studies, provides a rationale for the extensive cross-reactivity of b12 and a valuable framework for the design of HIV-1 vaccines capable of eliciting b12-like activity.