A neutralizing monoclonal antibody previously mapped exclusively on human immunodeficiency virus type 1 gp41 recognizes an epitope in p17 sharing the core sequence IEEE.
We report here that a human immunodeficiency virus type 1 (HIV-1)-specific neutralizing monoclonal antibody (MAb 1575) mapped to the conserved putative intracellular region from amino acid residues 735 to 752 (735-752 region) of gp41 also recognizes a region in an extracellular portion of p17. Both epitopes have a core recognition sequence (IEEE) in a nonhomologous context. The IEEE motif found in HIV-1 p17 is located in a region known as HGP-30 (residues 86 to 115) which has been previously associated with virus neutralization, cytotoxic T lymphocyte activity, and mother-to-child transmission. An analysis of available gp41 and p17 sequences demonstrates that in these regions both IEEE sequences are highly conserved in different HIV-1 clades. The presence of the IEEE epitope in p17 allows us to explain some unexpected neutralizing characteristics of MAb 1575. In addition, the gp41 735-752 region has been previously reported both in intra- and extracellular locations. Our results suggest that the extracellular location was the result of cross-reactivity with p17.
Buratti
E
E
International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
Tisminetzky
S G
SG
D'Agaro
P
P
Baralle
F E
FE
D000911:Antibodies, Monoclonal / Q000276:immunology; D002460:Cell Line; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D019084:Fluorescent Antibody Technique, Indirect; D005838:Genotype; D015483:HIV Antibodies / Q000276:immunology*; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D014407:Tumor Cells, Cultured; D054301:gag Gene Products, Human Immunodeficiency Virus
D000911:Antibodies, Monoclonal; D000939:Epitopes; C052407:HGP-30 peptide, Human immunodeficiency virus-1; D015483:HIV Antibodies; D015488:HIV Antigens; D015700:HIV Envelope Protein gp41; D010455:Peptides; D011993:Recombinant Fusion Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus