Linear and cyclic peptides mimicking the disulfide loops in HIV-2 envelope glycoprotein induced antibodies with different specificity.
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.
Jrad
B B
BB
Laboratoire d'Immuno-Virologie, Université Paul Sabatier, Toulouse, France.
Bahraoui
E
E
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
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