title: Linear and cyclic peptides mimicking the disulfide loops in HIV-2 envelope glycoprotein induced antibodies with different specificity.
abstract: The aim of this study was to compare the immunogenicity and antigenicity of cyclic and linear peptides that mimic the disulfide loops in HIV-2ROD gp125. Based on the hypothetical assignment of intrachain disulfide bonds in HIV-2 envelope glycoprotein, peptides expected to mimic all 11 disulfide-bonded domains were synthesized, oxidized or cysteine-alkylated; they were then purified and characterized. Rabbits were immunized with either linear cysteine-alkylated peptides (L1-L11) or cyclic oxidized peptides (C1-C11). All peptides except 7L elicited antibodies with titers between 10(3) and 5 x 10(6). Anti-peptide C (2, 3, 4, 7, 8, 9, 11) and anti-peptide L (2, 3, 8, 9, 11) antibodies recognized the native HIV-2 gp 125. Moreover, we found that cyclization of the peptides significantly increased the level of anti-peptide antibodies reacting with the intact antigen protein. Deglycosylation increased the level of protein reactivity of anti-peptide antibodies and rendered the epitopes in peptides 5, 6, 10 accessible, which were masked in the native protein. Peptide 1 induced antibodies reacting only with the denatured reduced gp125 HIV-2. In addition, while anti-peptide L antibodies reacted better with L peptide (called "linear" structural specificity), anti-peptide C antibodies reacted similarly with L and C peptides (called "broad" structural specificity). Interestingly, the "broad" structural specificity of antibodies correlated with reactivity against native gp125. Although none of these anti-peptide antisera displayed neutralizing activity against HIV-2ROD, these results support the hypothesis that the structural restriction of peptides have a major influence upon the generation of more specific antibodies for recognizing the intact protein.
authors.affiliation: Laboratoire d'Immuno-Virologie, Université Paul Sabatier, Toulouse, France.
authors.forename: B B
authors.initials: BB
authors.lastname: Jrad
authors.forename: E
authors.initials: E
authors.lastname: Bahraoui
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000918:Antibody Specificity; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology; D015686:Gene Products, env / Q000737:chemistry / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D008875:Middle Aged; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D011498:Protein Precursors / Q000737:chemistry / Q000276:immunology*; D011817:Rabbits; D054299:env Gene Products, Human Immunodeficiency Virus
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D015686:Gene Products, env; D010455:Peptides; D011498:Protein Precursors; D054299:env Gene Products, Human Immunodeficiency Virus; C066316:gp125 envelope protein, Human immunodeficiency virus 2