A predominant group-specific neutralizing epitope of human immunodeficiency virus type 1 maps to residues 342 to 511 of the envelope glycoprotein gp120.
Recombinant native human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins gp160 and gp120 (residues 1 to 511) expressed in insect cells quantitatively adsorbed the group-specific neutralizing antibodies found in human sera. However, these antibodies were not adsorbed by envelope fragment 1 to 471 or 472 to 857 or by both fragments sequentially, even though together they add up to the full-length gp160 sequence. A hybrid envelope glycoprotein was constructed with residues 342 to 511 of the HIV-1 sequence and residues 1 to 399 of the simian immunodeficiency virus type 1 sequence to vary the HIV-1 sequence while preserving its conformation. This hybrid glycoprotein quantitatively adsorbed human neutralizing antibodies, while native simian immunodeficiency virus type 1 envelope glycoprotein did not. These results identify a new neutralizing epitope that depends on conformation and maps to residues 342 to 511 of gp120. It overlaps the extended CD4-binding site but is distinct from the V3 loop described previously (K. Javaherian et al., Proc. Natl. Acad. Sci. USA 86:6768-6772, 1989; J. R. Rusche et al., Proc. Natl. Acad. Sci. USA 85:3198-3202). Since it is conserved among diverse HIV-1 isolates, this new epitope may be a suitable target for future vaccine development.
Berkower
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Molecular Immunology Laboratory, Food and Drug Administration, National Institutes of Health Campus, Bethesda, Maryland 20892.
Murphy
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D
Smith
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Smith
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GE
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000032:analysis*; D001666:Binding Sites, Antibody; D015704:CD4 Antigens / Q000276:immunology; D000939:Epitopes / Q000032:analysis / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D008961:Models, Structural; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011487:Protein Conformation; D055503:Protein Multimerization; D011817:Rabbits / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000235:genetics; D010948:Viral Plaque Assay
D000906:Antibodies; D000936:Antigen-Antibody Complex; D015704:CD4 Antigens; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins