HUMORAL IMMUNE-RESPONSE TO IMMUNOCOMPLEXED HIV ENVELOPE GLYCOPROTEIN-120

To further our understanding of the nature of HIV-1 immunogenicity, we injected mice with the virus envelope protein gp120 in different conf igurations: free, complexed with its receptor CD4, and as an immunocom plex with a monoclonal antibody directed against the V3 loop of the pr otein, Analyses of the polyclonal sera, as well as of monoclonal antib odies produced in each case, allowed us to conclude that the quality o f the humoral immune response depended on the complexation state of th e antigen. For the free gp120 and gp120-CD4 complex the responses were directed mainly toward conformational epitopes, However, gp120 immuno complexed with anti-V3 loop MAb produced, in addition, numerous MAbs d irected toward linear epitopes, Epitopes were mapped using immunoblots of gp120 cleaved with S. aureus V8 protease and a combinatorial epito pe phage-display library, It was found that some of the linear epitope s had been previously identified as T cell epitopes, These results sug gest that the immunocomplexed gp120 may be particularly well taken up by antigen-presenting cells, leading to the processing of the gp120 an d the efficient presentation of T cell epitopes, Thus immunocomplexati on should afford a means for enhancing the immunogenicity of gp120 and improving its presentation.