Fine specificity of antibody recognition may predict amino acid substitution in the third variable region of gp120 during HIV type 1 infection.
To investigate how human immunodeficiency virus type 1 (HIV-1) escapes from antibodies directed against the neutralization domain in the third variable region (V3) of gp120, we examined precisely which amino acid contributed to antibody binding. From six HIV-1-infected individuals, sequential sera were tested for antibody binding to individually designed peptide panels. Each individual panel contained all V3 domain sequences of cloned HIV-1 variants obtained at several time points from the studied individual. We showed that the V3 domain is a major site for escape of the humoral immune response. We showed antibody binding was reduced by certain mutations in the V3 domain and sometimes concerted mutations rendered very distinct antigenic variants. The position and the number of the mutations that occurred during infection corresponded with the position and number of amino acids in the V3 domain that were important for binding to anti-V3 antibodies in the early immune response. The specificity of the antibody binding hardly changed during infection. Although mutations at several positions of the V3 domain reduced antibody binding, the mutations were limited to certain positions, probably because the function of the region has to be maintained. The amino acids that were important for binding in combination with the preference for changes at certain positions predicted to some extent the mutations that occurred later during infection.
Langedijk
J P
JP
Institute for Animal Science and Health (ID-DLO), Lelystad, The Netherlands.
Zwart
G
G
Goudsmit
J
J
Meloen
R H
RH
D000595:Amino Acid Sequence; D000918:Antibody Specificity; D000939:Epitopes / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology*; D006679:HIV Seropositivity / Q000097:blood / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008137:Longitudinal Studies; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*
D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments