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 s trains. We analyzed the antibody reactivity of HIV-l-infected individu als from Argentina and Sweden to overlapping synthetic peptides coveri ng aa 647-684 of HIV-1 MN gp41. An immunodominant antigenic determinan t was discovered in the C-terminal region adjacent to the ELDKWA seque nce. Most of the sera from both Argentina and Sweden reacted only with peptides representing this region. Two other patterns of reactivity w ere also observed: some sera reacted only with peptides spanning the c entral region of gp41, including the ELDKWA sequence; other sera react ed with both the central and C-terminal regions. Differences in reacti vity were noted between Argentinian and Swedish sera in terms of pepti des covering the central region. In addition, to determine the amino a cids essential for antibody binding, seroreactivity against a set of s ubstitution peptides covering the immunodominant epitope was studied, Results obtained indicated that carboxyl amino acids WNWFDI close to t he ELDKWA sequence were the most important for antibody binding. Abili ty of sera, tested for peptide reactivity, to neutralize HIV-I was als o analyzed, High antibody reactivity to the central region was frequen tly found in sera with high neutralizing titers. This observation was not seen when seroreactivity to peptides spanning the C-terminal regio n was analyzed, These results suggest that the immunodominant epitope C terminal to the ELDKWA sequence is not involved in inducing neutrali zing antibodies.