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.
Expression of an HIV-1 infection-related idiotype/clonotype in antibodies directed to envelope glycoprotein gp 120 of HIV-1: Early and concomitant idiotype increase in antibodies against the homologous vaccine strain
TOVO, Pier Angelo;
1995-01-01
Abstract
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.
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