Antigenic implications of human immunodeficiency virus type 1 envelope quaternary structure: oligomer-specific and -sensitive monoclonal antibodies.

• DOI: 10.1073/pnas.91.24.11699
• Publication Date: 2006-05-31T12:59:41Z
• Authors: C C Broder; P L Earl; D Long; S T Abedon; B Moss; R W Doms
• Keywords: 0301 basic medicine; HIV Antigens; Macromolecular Substances; Protein Conformation; Antibodies, Monoclonal; HIV Envelope Protein gp120; HIV Envelope Protein gp41; 3. Good health; Mice; 03 medical and health sciences; Viral Envelope Proteins; Neutralization Tests; HIV-1; Animals; Humans; Epitope Mapping

A majority of monoclonal antibodies (mAbs) raised against soluble oligomeric human immunodeficiency virus type 1 isolate IIIB (HIV-1IIIB) envelope (env) glycoprotein reacted with conformational epitopes within the gp120 or gp41 subunits. Of 35 mAbs directed against gp41, 21 preferentially reacted with oligomeric env. A subset of these mAbs reacted only with env oligomers (oligomer-specific mAbs). In contrast, only 1 of 27 mAbs directed against the gp120 subunit reacted more strongly with env oligomers than with monomers, and none were oligomer-specific. However, 50% of anti-gp120 mAbs preferentially recognized monomeric env, suggesting that some epitopes in gp120 are partially masked or altered by intersubunit contacts in the native env oligomer. Two mAbs to oligomer-dependent epitopes in gp41 neutralized HIV-1IIIB and HIV-1SF2, and binding of these mAbs to env was blocked by preincubation with HIV-1-positive human serum. Thus, immunization with soluble, oligomeric env elicits antibodies to conserved, conformational epitopes including a newly defined class of neutralizing antibodies that bind to oligomer-specific epitopes in gp41, and may also minimize the production of antibodies that preferentially react with monomeric env protein.