The 'repertoire freeze hypothesis' describing the persistence of clonal responses to HIV-1 antigens during the course of infection has been considered as a major factor in the pathogenesis of AIDS. This hypothesis predicts that the clonal response is shaped by the first encounter with HIV-1 antigens (clonal imprinting) and that a clonally dominant response inhibits subsequent responses to emerging virus variants. In the present study we have used a cross-reactive idiotype, called 1F7, as a marker to track the clonal composition of anti-HIV-1 antibodies induced by the first challenge with HIV-1 antigens in three samples of sera from (1) HIV seronegative volunteers vaccinated with recombinant rgp120 IIIB and MN, (2) experimentally HIV-1 (IIIB)-infected chimpanzees, and (3) naturally HIV-1-infected babies. We find that the idiotype appears concomitantly or delayed to the first detectable anti-gp120 antibody response. In HIV-infected, seroconverting babies 1F7 was expressed on antibodies directed to recombinant gp120 IIIB, MN, and SF2 as well as to peptide(s) homologous to the V3-loop of gp120 IIIB, MN, and SF2. In contrast to the equally distributed 1F7 idiotype expression on antibodies directed to gp120 IIIB, MN, and SF2 in naturally HIV-infected individuals, the 1F7 idiotype was expressed predominantly on anti-gp124) IIIB antibodies in HIV seronegative vaccinees primed with rgp120 IIIB and in HIV-1 IIIB-infected chimpanzees. These findings indicate that the 1F7 idiotype is a marker for the initially induced antibody response that will dominate during the course of vaccination or infection and can be reinforced by variant rgp120 and HIV-1 strains, respectively. Furthermore, if clonal persistence is a major cause for the failure of the immune response to adapt to emerging virus variants, then current recombinant envelope subunit vaccines may promote immune escape HIV variants once infection occurs.
|Original language||English (US)|
|Number of pages||15|
|State||Published - Aug 29 1995|
ASJC Scopus subject areas
- Microbiology (medical)