PMID- 9820146 OWN - NLM STAT- MEDLINE DCOM- 19981207 LR - 20061115 IS - 0022-1317 (Print) IS - 0022-1317 (Linking) VI - 79 ( Pt 11) DP - 1998 Nov TI - The neutralizing antibody response against a conserved region of human immunodeficiency virus type 1 gp41 (amino acid residues 731-752) is uniquely directed against a conformational epitope. PG - 2709-16 AB - Amino acids 731-752 (731PRGPDRPEGIEEEGGERDRDRS752) of the transmembrane glycoprotein gp41 of human immunodeficiency virus type 1 (HIV-1) are conserved in most virus isolates and are controversially reported to be implicated in virus neutralization. The humoral response in infected patients against this region is poor and humans immunized with gp160 show high levels of antibodies against the peptide but poor neutralization titres. Nonetheless, several groups have succeeded in obtaining neutralizing antibodies against this sequence using different antigen-presenting systems. In order to identify the sequence(s) against which the neutralizing response was generated, we used the flock house virus (FHV) antigen-presenting system to analyse neutralizing antisera from mice immunized with a cowpea mosaic virus (CPMV) chimera expressing the 731-752 sequence. Data show that the neutralizing response is uniquely directed against a conformational epitope mapping to the ERDRD portion of this sequence, although the major antibody response, which is non-linear, and is not neutralizing, is against an IEEE epitope. These results provide an explanation for the controversy regarding the immunogenicity of this region of gp41 and suggest that this conformational epitope, in the absence of the non-neutralizing epitope, should be considered for a subunit vaccine. In addition, this study highlights the usefulness of antigen-presenting systems that preserve epitope conformation in the investigation of immune responses. FAU - Buratti, E AU - Buratti E AD - International Centre for Genetic Engineering and Biotechnology, Padriciano, Trieste, Italy. FAU - McLain, L AU - McLain L FAU - Tisminetzky, S AU - Tisminetzky S FAU - Cleveland, S M AU - Cleveland SM FAU - Dimmock, N J AU - Dimmock NJ FAU - Baralle, F E AU - Baralle FE LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Gen Virol JT - The Journal of general virology JID - 0077340 RN - 0 (Antibodies, Viral) RN - 0 (HIV Envelope Protein gp41) RN - 0 (Immunodominant Epitopes) SB - IM MH - Animals MH - Antibodies, Viral/*immunology MH - Antibody Specificity MH - HIV Envelope Protein gp41/chemistry/*immunology MH - HIV-1/*immunology MH - Humans MH - Immunodominant Epitopes/*chemistry/immunology MH - Mice MH - Protein Conformation EDAT- 1998/11/20 00:00 MHDA- 1998/11/20 00:01 CRDT- 1998/11/20 00:00 PHST- 1998/11/20 00:00 [pubmed] PHST- 1998/11/20 00:01 [medline] PHST- 1998/11/20 00:00 [entrez] AID - 10.1099/0022-1317-79-11-2709 [doi] PST - ppublish SO - J Gen Virol. 1998 Nov;79 ( Pt 11):2709-16. doi: 10.1099/0022-1317-79-11-2709.