Specificity of antibodies produced against native or desialylated human immunodeficiency virus type 1 recombinant gp160.
In a previous report we have shown that, in contrast to antibodies produced against native or fully deglycosylated human immunodeficiency virus type 1 (HIV-1) gp160 in rabbits, antibodies raised against desialylated HIV-1 gp160 also recognize gp140 from HIV-2 at high titers. Here, we characterize the fine specificity of these cross-reactive antibodies. Inhibition assays with a panel of synthetic peptides as competitors showed that cross-reactivity to gp140 was due to antibodies that were specific for the region encompassing HIV-1 gp41 immunodominant epitope, mimicked by peptide P39 (residues 583 to 609), the latter being able to totally inhibit the formation of complexes between radiolabeled HIV-2 gp140 and antibodies elicited by desialylated HIV-1 gp160. In addition, anti-desialylated gp160 antibodies retained on a P39 affinity column still bound HIV-2 gp140. Fine mapping has enabled us to localize the cross-reactive epitope within the N-terminal extremity of the gp41 immunodominant region. Interestingly, this cross-reactive antibody population did not recognize glycosylated or totally deglycosylated simian immunodeficiency virus gp140 despite an amino acid homology with HIV-1 within this region that is comparable to that of HIV-2. This cross-reactivity between HIV-1 and HIV-2 did not correlate with cross-neutralization. These results illustrate the influence of carbohydrate moieties on the specificity of the antibodies produced and clearly indicate that such procedures may be an efficient way to raise specific immune responses that are not type specific. Moreover, this cross-reactivity might explain the double-positive reactivity observed, in some human sera, against both HIV-1 and HIV-2 envelope antigens.
Benjouad
A
A
Centre National de la Recherche Scientifique URA 1455, Laboratoire de Biochimie, Faculté de Médecine Nord, Marseille, France.
Gluckman
J C
JC
Montagnier
L
L
Bahraoui
E
E
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000032:analysis; D000918:Antibody Specificity / Q000276:immunology*; D001667:Binding, Competitive; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology; D015686:Gene Products, env / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid; D010446:Peptide Fragments / Q000276:immunology; D011498:Protein Precursors / Q000276:immunology*; D012794:Sialic Acids / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus
D000914:Antibodies, Viral; D000939:Epitopes; D015686:Gene Products, env; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D011498:Protein Precursors; D012794:Sialic Acids; D054299:env Gene Products, Human Immunodeficiency Virus; C066315:gp140 envelope protein, Human immunodeficiency virus 2; D019158:N-Acetylneuraminic Acid