Mapping the B cell superantigen binding site for HIV-1 gp120 on a V(H)3 Ig.

Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

Mapping the B cell superantigen binding site for HIV-1 gp120 on a V(H)3 Ig.

Int Immunol. 2000 Mar;12(3):305-12. Unique Identifier : AIDSLINE MED/20166982
Neshat MN; Goodglick L; Lim K; Braun J; Department of Pathology and Laboratory Medicine, and The; Molecular Biology Institute, University of California-Los; Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095-1732, USA.

Abstract: The emerging class of B cell superantigens includes HIV-1 gp120, which binds to many members of the V(H)3 Ig gene family. The present study addresses the structural features of V(H)3 antibodies conferring gp120 binding activity using a panel of recombinant full-length and Fab Ig proteins. Binding activity was fully conferred by the Fab portion of the Ig molecule. The V(H) region was the major determinant of binding; diverse light chains were permissive for gp120 binding. A series of recombinant V(H)3-V(H)1 chimeric molecules was created to analyze the contribution of different subregions of V(H)3 to gp120 binding. Hypervariable loop 1 (H1) substitution alone caused a 10-fold reduction in binding activity. The framework subregions (FR1, FR2 and FR3) and H2 also influenced binding, since substitutions of various combinations of these subregions conferred 10- to 100-fold binding reductions. We conclude that gp120 binding occurs through a non-conventional interaction involving multiple discontinuously arrayed residues spanning the V(H), and including roles in gp120 contact and favorable conformation of the V(H).

Keywords: JOURNAL ARTICLE Amino Acid Sequence Amino Acid Substitution Animal Antibodies, Monoclonal/CHEMISTRY/GENETICS/*IMMUNOLOGY Antigen-Antibody Reactions B-Lymphocytes/*IMMUNOLOGY Binding Sites, Antibody/GENETICS/*IMMUNOLOGY Genes, Immunoglobulin HIV Antibodies/CHEMISTRY/GENETICS/*IMMUNOLOGY HIV Envelope Protein gp120/*IMMUNOLOGY HIV-1/*IMMUNOLOGY Immunoglobulin Variable Region/CHEMISTRY/GENETICS/*IMMUNOLOGY Immunoglobulins, Fab/CHEMISTRY/GENETICS/IMMUNOLOGY Immunoglobulins, Heavy-Chain/CHEMISTRY/GENETICS/*IMMUNOLOGY Mice Molecular Sequence Data Recombinant Fusion Proteins/CHEMISTRY/GENETICS/IMMUNOLOGY Sequence Alignment Sequence Homology, Amino Acid Superantigens/*IMMUNOLOGY Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S.
000730
A0071481

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