Immunodominant B-cell clones responsive to an HIV-1 neutralization and cell fusion inhibition epitope in chimpanzee-to-chimpanzee passages of HTLV-IIIB and LAV-1.

Chimpanzees infected with the HIV-1 strains HTLV-IIIB or LAV-1 in primary, secondary or tertiary passages developed neutralizing antibodies binding to variable domain V3 in the carboxyl terminal half of the external envelope (amino acids 309-317). Nonapeptide antigens reflecting either the HTLV-IIIB/LAV-1 neutralization epitope (IQRGPGRAF, designated 3B) or peptide analogues (ITKGPGRVI, designated RF; IQRGPGRVI, designated 3B/RF; ITKGPGRAF, designated RF/3B) were previously shown to be able to distinguish antibody populations in a polyclonal response of rabbits to these peptides. Sera from chimpanzees infected with the HIV-1 strains HTLV-IIIB and LAV-1 were tested for the presence of antibodies reactive to these nonapeptides. Sera from 3 chimpanzees infected with a primary LAV-1 or HTLV-IIIB passage, 2 chimpanzees infected with blood from the primary infected chimpanzees and from 1 chimpanzee infected with blood from a secondary passage animal, all bound peptides 3B and 3B/RF, sharing the sequence IQRGPGR, in equally high tires. In 2 primary passage animals and in 1 secondary passage animal, the capacity to bind to peptides 3B and 3B/RF was equally high, indicating clonality of these B-cell responses. Contrasting results were obtained with the sera from 1 primary, 1 secondary and 1 tertiary passage animal, showing stronger binding to the 3B/RF peptide than to the 3B peptide. The animals with antibodies binding strongly to the 3B peptide had an early HTLV-IIIB-induced cell-fusion-inhibiting (CFI) antibody response, while the animals with antibodies binding strongly to the 3B/RF peptide had a late HTLV-IIIB-induced CFI antibody response. This difference in binding to the 3B peptide might result from antigenic variation in the neutralization domain of the inoculum virus(es). The conservation of the antibody specificity for the neutralization epitope of the inoculum strain might open the way to type circulating virus strains by antibody specificity for a panel of peptide analogues derived from the V3 domain of the external envelope of distinct HIV-1 strains.