Immunodominant glycoprotein 41 epitope identified by seroreactivity in HIV type 1-infected individuals.
A highly conserved gp41 epitope (amino acid sequence ELDKWA) has been described to elicit antibodies neutralizing a broad variety of HIV-1 strains. We analyzed the antibody reactivity of HIV-1-infected individuals from Argentina and Sweden to overlapping synthetic peptides covering aa647-684 of HIV-1 MN gp41. An immunodominant antigenic determinant was discovered in the C-terminal region adjacent to the ELDKWA sequence. Most of the sera from both Argentina and Sweden reacted only with peptides representing this region. Two other patterns of reactivity were also observed: some sera reacted only with peptides spanning the central region of gp41, including the ELDKWA sequence; other sera reacted with both the central and C-terminal regions. Differences in reactivity were noted between Argentinian and Swedish sera in terms of peptides covering the central region. In addition, to determine the amino acids essential for antibody binding, seroreactivity against a set of substitution peptides covering the immunodominant epitope was studied. Results obtained indicated that carboxyl amino acids WNWFDI close to the ELDKWA sequence were the most important for antibody binding. Ability of sera, tested for peptide reactivity, to neutralize HIV-1 was also analyzed. High antibody reactivity to the central region was frequently found in sera with high neutralizing titers. This observation was not seen when seroreactivity to peptides spanning the C-terminal region was analyzed. These results suggest that the immunodominant epitope C terminal to the ELDKWA sequence is not involved in inducing neutralizing antibodies.
Calarota
S
S
Department of Microbiology, University of Buenos Aires School of Medicine, Argentina.
Jansson
M
M
Levi
M
M
Broliden
K
K
Libonatti
O
O
Wigzell
H
H
Wahren
B
B
D000595:Amino Acid Sequence; D018604:Epitope Mapping; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes; D008297:Male; D008969:Molecular Sequence Data; D009500:Neutralization Tests
D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D016056:Immunodominant Epitopes