International Immunology, Vol. 12, No. 3, 305-312,
March 2000
© 2000 Japanese Society for Immunology
Mapping the B cell superantigen binding site for HIV-1 gp120 on a VH3 Ig
Department of Pathology and Laboratory Medicine, and
1 The Molecular Biology Institute, University of California–Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095-1732, USA
Correspondence to: J. Braun
The emerging class of B cell superantigens includes HIV-1 gp120, which binds to many members of the VH3 Ig gene family. The present study addresses the structural features of VH3 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 VH region was the major determinant of binding; diverse light chains were permissive for gp120 binding. A series of recombinant VH3–VH1 chimeric molecules was created to analyze the contribution of different subregions of VH3 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 VH, and including roles in gp120 contact and favorable conformation of the VH.
Keywords: gp120, HIV-1, Ig, Protein A, superantigen, VH gene family
The first two authors contributed equally to this work
Transmitting editor: K. L. Knight
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