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- Title
Mapping the B cell superantigen binding site for HIV-1 gp120 on a V(H)3 Ig.
- Authors
Neshat, M N; Goodglick, L; Lim, K; Braun, J
- 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).
- Publication
International immunology, 2000, Vol 12, Issue 3, p305
- ISSN
0953-8178
- Publication type
Journal Article
- DOI
10.1093/intimm/12.3.305