Specificity and function of the individual amino acids of an important determinant of human immunodeficiency virus type 1 that induces neutralizing activity.
An important antigenic determinant of human immunodeficiency virus type 1 that induces neutralizing activity in infected humans and chimpanzees was previously mapped with nonapeptides between amino acids 307 and 320 on the external envelope glycoprotein (gp 120) of strain HTLV-IIIB (molecular clone BH10) and amino acids 320 to 330 of strain HTLV-IIIRF. Using different sera we found different reactive nonapeptides that overlapped and shared a tetrapeptide, GPGR. This tetrapeptide, which is the same in HTLV-IIIB and HTLV-IIIRF, is flanked by amino acids that vary between virus strains. Because GPGR is predicted to form a beta-turn and is flanked by two cysteine residues that may form a disulphide bridge, a hairpin-like structure is suggested for this part of gp120. The tetrapeptide GPGR and the reactive peptides are located on top of this structure, well exposed to antibodies. We determined the role of the individual amino acids in antibody binding using three sets of peptide analogues derived from three reactive nonapeptides (two of strain HTLV-IIIB which overlapped and one of strain HTLV-IIIRF). Each set contained peptide analogues in which each amino acid was replaced, one at a time, by all genetically encoded amino acids. At least five consecutive amino acids in each nonapeptide were essential for antibody binding. They include amino acids of GPGR and potentially provide the virus with ample opportunity to escape immune surveillance.
Meloen
R H
RH
Central Veterinary Institute, Lelystad, The Netherlands.
Liskamp
R M
RM
Goudsmit
J
J
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology*; D015699:HIV Envelope Protein gp120; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D015394:Molecular Structure; D009500:Neutralization Tests; D009842:Oligopeptides / Q000276:immunology; D002679:Pan troglodytes; D010449:Peptide Mapping; D012191:Retroviridae Proteins / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology
D000596:Amino Acids; D000939:Epitopes; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D009842:Oligopeptides; D012191:Retroviridae Proteins; D014759:Viral Envelope Proteins