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F3.9F: To examine sequence and conformational differences between subtypes B and C, several experiments were performed with 11 MAbs regarding binding and neutralization. Both binding and neutralization studies revealed that the 11 MAbs could be divided in three different groups, and that the most differences between the subtypes were located in the stem and turn regions of V3. F3.9F belonged to the group 1 MAbs, which are able to bind both subtype B and C gp120 proteins and peptides. F3.9F was also able to bind both subtype C V3 in the subtype B Env backbone chimera, and reverse, indicating that F3.9F binds to V3 in a way that is not affected by the gp120 backbone. For subtype B, changes in the position 13 (H13R) and/or position 18 (R18Q) showed no difference of F3.9F binding compared to wildtype. For subtype C, H13 residue enhanced binding of F3.9F, but the R18 mutation reduced binding, indicating that R18 affects the conformation of V3 subtype C. Although F3.9F bound to JR-FL V3, this isolate was resistant to neutralization by F3.9F. F3.9F was able to neutralize SF-162, and a chimeric SF162 variant with a JR-FL-like V3 sequence was hypersensitive to neutralization by this Ab.
Patel2008
(neutralization, binding affinity, subtype comparisons)
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F3.9F: Of 35 Env-specific MAbs tested, only 2F5, 4E10, IgG1b12, and two CD4BS adjacent MAbs (A32 and 1.4G) and gp41 MAbs (2.2B and KU32) had binding patterns suggesting polyspecific autoreactivity, and similar reactivities may be difficult to induce with vaccines because of elimination of such autoreactivity. F3.9F has no indication of polyspecific autoreactivity.
Haynes2005
(autoantibody or autoimmunity)
References
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2 references.
Haynes2005
Barton F. Haynes, Judith Fleming, E. William St. Clair, Herman Katinger, Gabriela Stiegler, Renate Kunert, James Robinson, Richard M. Scearce, Kelly Plonk, Herman F. Staats, Thomas L. Ortel, Hua-Xin Liao, and S. Munir Alam. Cardiolipin Polyspecific Autoreactivity in Two Broadly Neutralizing HIV-1 Antibodies. Science, 308(5730):1906-1908, 24 Jun 2005. Comment in Science 2005 Jun 24;308(5730):1878-9. PubMed ID: 15860590.
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Patel2008
Milloni B Patel, Noah G. Hoffman, and Ronald Swanstrom. Subtype-Specific Conformational Differences within the V3 Region of Subtype B and Subtype C Human Immunodeficiency Virus Type 1 Env Proteins. J. Virol., 82(2):903-916, Jan 2008. PubMed ID: 18003735.
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