B cell epitope mapping of human immunodeficiency virus envelope glycoproteins with long (19- to 36-residue) synthetic peptides.
Envelope glycoproteins, gp 120 and gp41, of the human immunodeficiency virus type 1 (HIV-1) elicit immune responses, including virus-neutralizing antibodies, which are expected to play a role in the defence against HIV-1 infection. Subregions of the gp120/gp41 sequence have immunosuppressive effects or may be implicated in autoimmune responses. Some of the immunodominant epitopes of gp120/gp41 do not contribute to protective immunity and act as immunological decoys. These circumstances emphasize the need to select from gp120/gp41 regions inducing protective responses. Towards this goal, 30 peptides covering approximately 87% of the HIV-1 strain BH10 gp120/gp41 sequence were synthesized. Antibodies in rabbit and human anti-HIV-1 sera recognized 28 and nine of the peptides, respectively, indicating that most of the gp120/gp41 sequence is immunogenic and secondly, that the antibody response to HIV-1 is restricted in infected humans. Most of the peptides, without conjugation to carriers, elicited high levels of anti-peptide (endpoints 1: greater than 10(4] and anti-gp120/gp41 (endpoints 1: greater than or equal to 10(3] antibodies. The highest levels of virus-neutralizing antibodies were elicited by peptide 306 to 338 from a hypervariable loop of gp120. Additional peptides from the full-length hypervariable loop (303 to 338) of HIV-1 BH10 and from 20 additional HIV-1 isolates were recognized differentially by human anti-HIV, suggesting that success of passive immunization may depend on a match between administered antibodies and the challenging HIV-1 strain, and also that active immunization with selected peptides from a hypervariable region of distinct HIV-1 isolates should be explored further as a method for prophylaxis against infection.
Lindsley F. Kimball Research Institute, New York Blood Center, New York 10021.
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Neurath
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Strick
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Lee
D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology; D015153:Blotting, Western; D003124:Colorimetry; D000939:Epitopes / Q000032:analysis*; D015483:HIV Antibodies / Q000032:analysis; D015488:HIV Antigens / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000276:immunology; D010449:Peptide Mapping; D011863:Radioimmunoassay
D000939:Epitopes; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D007106:Immune Sera; D010446:Peptide Fragments