Abstract
Antibodies to conserved epitopes on the human immunodeficiency virus (HIV) surface protein gp140 can protect against infection in non-human primates, and some infected individuals show high titres of broadly neutralizing immunoglobulin (Ig)G antibodies in their serum. However, little is known about the specificity and activity of these antibodies. To characterize the memory antibody responses to HIV, we cloned 502 antibodies from HIV envelope-binding memory B cells from six HIV-infected patients with broadly neutralizing antibodies and low to intermediate viral loads. We show that in these patients, the B-cell memory response to gp140 is composed of up to 50 independent clones expressing high affinity neutralizing antibodies to the gp120 variable loops, the CD4-binding site, the co-receptor-binding site, and to a new neutralizing epitope that is in the same region of gp120 as the CD4-binding site. Thus, the IgG memory B-cell compartment in the selected group of patients with broad serum neutralizing activity to HIV is comprised of multiple clonal responses with neutralizing activity directed against several epitopes on gp120.
Publication types
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibody Affinity
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B-Lymphocytes / immunology*
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Binding Sites
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CD4 Antigens / metabolism
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Enzyme-Linked Immunosorbent Assay
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Epitope Mapping
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Epitopes, B-Lymphocyte / chemistry
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Epitopes, B-Lymphocyte / immunology
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HIV Antibodies / analysis*
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HIV Antibodies / immunology*
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HIV Antibodies / isolation & purification
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HIV Envelope Protein gp120 / chemistry
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HIV Envelope Protein gp120 / immunology
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HIV Envelope Protein gp120 / metabolism
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HIV Envelope Protein gp41 / chemistry
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HIV Envelope Protein gp41 / immunology
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HIV Infections / immunology*
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Humans
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Immunologic Memory / immunology*
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Neutralization Tests
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Receptors, HIV / metabolism
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Viral Load
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env Gene Products, Human Immunodeficiency Virus / chemistry
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env Gene Products, Human Immunodeficiency Virus / immunology*
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env Gene Products, Human Immunodeficiency Virus / metabolism
Substances
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CD4 Antigens
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Epitopes, B-Lymphocyte
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HIV Antibodies
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HIV Envelope Protein gp120
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HIV Envelope Protein gp41
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Receptors, HIV
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env Gene Products, Human Immunodeficiency Virus
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gp140 envelope protein, Human immunodeficiency virus 1