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J P Corre

Publications and source records attributed to J P Corre.

3 recordsLinked to original sources

Conserved structural features between HLA-DO beta and -DR beta.

HLA-DO is a non-classical MHC class II molecule presumed to play a specialized role in the antigen processing pathway. We have modeled the HLA-DO beta-chain and found its overall structure compatible with the one of DR beta. Functional studies further highlighted the similarity between these beta-chains of the class II family of proteins. Indeed, a mixed heterodimer composed of the DR alpha and a chimeric DO beta-chains presented bacterial superantigens to T cells and was shown to interact with CD4. The implications of such structural conservation for the in vivo functions of HLA-DO are discussed.

Amino Acid Sequence↗

Idiotypic expression of anti-gp120 antibodies in unrelated human immunodeficiency virus-infected individuals.

Although it is recognized that human immunodeficiency virus (HIV) env genes exhibit a high degree of variability, little is known about the molecular heterogeneity of gp120-specific antibodies in infected individuals. As a first step to approach this issue, we investigated the idiotypic relatedness of anti-gp120 antibodies present in the serum of HIV-infected individuals. Idiotypic determinants (idiotopes) are fingerprints of the variable region of the antibody molecule and, as such, they represent unique probes with which to explore the diversity of the immune response. We isolated IgG anti-gp120 antibodies from the serum of a seropositive asymptomatic individual by affinity chromatography. The purified antibodies were shown to bind gp120 and gp160 by ELISA, Western blotting and radio-immunoprecipitation. They also recognized HIV-infected human T cells as detected by immunofluorescence. Anti-idiotypic reagents were generated against this gp120 idiotype, and one of them was used to study anti-gp120 idiotypic diversity in a panel of 65 sera drawn from AIDS and AIDS-related complex patients, and from HIV seropositive asymptomatic individuals. Sixty normal human sera were used as negative controls. We found no evidence for common idiotopes on anti-gp120 antibodies of unrelated individuals. In contrast, we also noticed that the idiotypic profile expressed sequentially at two different intervals in a persistently infected individual showed little variation. Finally, when the diversity of murine anti-gp120 antibodies with a monoclonal anti-idiotype was analysed, no evidence of cross-reactive idiotopes in the murine system was found.

Adult↗

Anti-idiotypic antibodies to human anti-gp120 antibodies bind recombinant and cellular human CD4.

The presence of anti-CD4 antibodies in sera of human immunodeficiency virus (HIV)-seropositive individuals has been recently documented, but its origin remains unknown. To test the hypothesis that anti-idiotypic antibodies to gp120, the HIV envelope glycoprotein with high affinity for CD4, mimic the configuration of gp120 and bind CD4, we performed two sets of experiments. First, we tested the possibility that anti-CD4 antibodies present in sera of a proportion of HIV-positive individuals exhibit variable region complementarity to autologous anti-gp120 antibodies. We show here that affinity-purified human anti-gp160 antibodies recognize specifically autologous affinity-purified anti-CD4 antibodies. We also demonstrate that antibodies to CD4 competitively inhibit anti-gp160 autologous antibodies binding to gp160. This implies that at least some anti-CD4 antibodies are directed towards idiotypic motifs located on anti-gp120 antibodies and that they may result from an anti-idiotypic response to anti-gp120 antibodies. In a second set of experiments, we examined the effect of anti-idiotypic immunization of experimental animals against human anti-gp120 antibodies. We found that anti-idiotypic antibodies produced in a rabbit immunized against affinity-purified human anti-gp120 antibodies specifically recognize recombinant and cellular human CD4, and that this interaction is competitively inhibited by soluble CD4. The data support the concept of idiotypic mimicry whereby anti-idiotypic antibodies produced against anti-gp120 antibodies recognize CD4, the cellular receptor of HIV.

Antibodies, Anti-Idiotypic↗