1. Characterization of a novel human immunodeficiency virus type 1 neutralizable epitope within the immunodominant region of gp41.
- Author
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Viveros M, Dickey C, Cotropia JP, Gevorkian G, Larralde C, Broliden K, Levi M, Burgess A, Cao C, Weiner DB, Agadjanyan MG, and Ugen KE
- Subjects
- Amino Acid Sequence, Amino Acid Substitution, Animals, Antibodies, Monoclonal immunology, Antibody Specificity immunology, Cell Line, Cysteine immunology, Cysteine metabolism, Disulfides immunology, Disulfides metabolism, HIV Antigens chemistry, HIV Envelope Protein gp160 immunology, HIV Envelope Protein gp41 chemistry, HIV Seropositivity immunology, HIV Seropositivity virology, HIV-1 genetics, HIV-1 physiology, Humans, Immune Sera immunology, Immunodominant Epitopes chemistry, Molecular Sequence Data, Neutralization Tests, Peptides, Cyclic chemical synthesis, Peptides, Cyclic chemistry, Peptides, Cyclic immunology, Rabbits, Virus Replication, HIV Antigens immunology, HIV Envelope Protein gp41 immunology, HIV-1 immunology, Immunodominant Epitopes immunology
- Abstract
Previously, we generated human monoclonal antibodies using peripheral blood mononuclear cells from an asymptomatic human immunodeficiency virus type 1 (HIV-1)-seropositive donor. One of these monoclonal antibodies (designated clone 3, CL3) recognized 10 amino acids (GCSGKLICTT) within the immunodominant region (cluster I) of the transmembrane envelope glycoprotein gp41 and neutralized infection of target cells with different laboratory isolates. Because the epitope recognized by CL3 has two cysteine residues that could potentially produce a disulfide loop in gp41, we analyzed binding of our monoclonal antibody to the cyclic and linear motif of the peptide sequence IWGCSGKLICTTAVP (residues 600-614). The CL3 antibody did not bind to the synthetic cyclic peptide but did recognize the linear form. Two polyclonal rabbit sera against both the linear and cyclic peptides were then generated. Both antisera bound to viral glycoproteins gp41 and gp160, but neither sera neutralized HIV-1 laboratory isolates. Using a set of alanine-substituted IWGCSGKLICTTAV peptides, we analyzed binding of polyclonal antisera and CL3. The profile of binding of polyclonal antisera to these peptides was different from that of CL3 to the same peptides. This suggests that CL3 recognized a unique neutralizable core epitope, which was not immunogenic in either the cyclic or the linear IWGCSGKLICTTAVP peptides used as immunogens in the rabbits., (Copyright 2000 Academic Press.)
- Published
- 2000
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