Antigenic implications of human immunodeficiency virus type 1 envelope quaternary structure: oligomer-specific and -sensitive monoclonal antibodies.
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.
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
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Broder
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Earl
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Abedon
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018604:Epitope Mapping; D015488:HIV Antigens / Q000737:chemistry*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D009500:Neutralization Tests; D011487:Protein Conformation; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology
D000911:Antibodies, Monoclonal; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D046911:Macromolecular Substances; D014759:Viral Envelope Proteins