Analysis of a highly immunodominant epitope in the human immunodeficiency virus type 1 transmembrane glycoprotein, gp41, defined by a human monoclonal antibody.
A human monoclonal antibody, 41-7 [immunoglobulin G1(kappa)], directed against the transmembrane glycoprotein gp41 of the human immunodeficiency virus type 1 (HIV-1) has been produced by direct fusion of lymph node cells from an HIV-1-infected individual with a human B-lymphoblastoid cell line. The minimal essential epitope for 41-7 was mapped to a conserved seven-amino acid sequence, N-CSGKLIC-C, located within the N-terminal part of gp41. Antibodies blocking the binding of 41-7 could be detected in the serum of all HIV-1-infected individuals tested, irrespective of the stage of the infection. The epitope is located externally to the plasma membrane, and it is accessible to antibody in the native conformation of the glycoprotein. Despite this, no neutralizing activity of 41-7 could be demonstrated in vitro. These data indicate, directly and indirectly, that this immunodominant epitope on gp41, although exposed on the viral surface, elicits antibodies lacking antiviral activity and, hence, should be avoided in future vaccine candidates.
Bugge
T H
TH
Laboratory of Tumor Virology, Fibiger Institute, Danish Cancer Society, Copenhagen.
Lindhardt
B O
BO
Hansen
L L
LL
Kusk
P
P
Hulgaard
E
E
Holmbäck
K
K
Klasse
P J
PJ
Zeuthen
J
J
Ulrich
K
K
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000302:isolation & purification; D015153:Blotting, Western; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000032:analysis*; D005455:Fluorescent Antibody Technique; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology*; D006679:HIV Seropositivity; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010455:Peptides / Q000138:chemical synthesis; D011994:Recombinant Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015700:HIV Envelope Protein gp41; D010455:Peptides; D011994:Recombinant Proteins