Carrier-dependent specificity of antibodies to a conserved peptide determinant of gp120.
Amino acid residues 421-436 constitute a comparatively conserved determinant of gp120 that participates in the binding of host cell CD4 receptors by HIV-1. We compared the immunogenicity of synthetic Cys-gp120 (421-436) conjugated to KLH via the N terminal Cys residue (KLH-I) and gp120 (421-436) extended at its N terminus with a 15 residue tetanus toxoid T cell epitope (T-I) in non-autoimmune mice (BALB/cstrain) and Fas-defective autoimmune mice (MRL/lpr strain). Both immunogens elicited high titer Abs detected as the binding to gp120 (421-436) conjugated to bovine serum albumin (BSA-I) immobilized in ELISA plates. Abs from KLH-I immunized mice displayed binding to full-length gp120 but the Abs from T-I immunized mice did not. Proteins unrelated in sequence to gp120 did not bind the Abs. Soluble I and T-I failed to compete with immobilized BSA-I for binding to anti-KLH-I Abs, whereas these peptides inhibited anti-T-I Ab binding by BSA-I (rank potency order: BSA-I > T-I >> I). These results indicate the influence of the carrier protein on the specificity of Abs to synthetic I. Low level BSA-I and gp120 binding Abs were detected in sera from non-immunized MRL/lpr mice. Similar Ab binding titers and specificity profiles were evident in MRL/lpr and BALB/c mice following immunization with KLH-I and T-I, indicating that pre-existing immunity to gp120 in the former strain does not influence the magnitude or specificity of the Ab response.
Karle
S
S
Department of Pathology and Internal Medicine, Chemical Immunology and Therapeutics Research Center, University of Texas, Houston Medical School, Houston, TX 77030, USA.
Nishiyama
Y
Y
Taguchi
H
H
Zhou
Y-X
YX
Luo
J
J
Planque
S
S
Hanson
C
C
Paul
S
S
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D002417:Cattle; D004337:Drug Carriers; D000939:Epitopes / Q000276:immunology*; D005260:Female; D015483:HIV Antibodies / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006433:Hemocyanins / Q000276:immunology*; D006801:Humans; D007114:Immunization; D018796:Immunoconjugates / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology*; D012710:Serum Albumin, Bovine / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D019014:fas Receptor / Q000235:genetics
D004337:Drug Carriers; D000939:Epitopes; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; C478240:HIV envelope protein gp120 (421-436); D018796:Immunoconjugates; D010446:Peptide Fragments; D013745:Tetanus Toxoid; D019014:fas Receptor; D012710:Serum Albumin, Bovine; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin