No abstract

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

The aim of this study was to investigate the epitope recognition pattern of La(SS-B) autoantibodies in sera from patients with Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) using overlapping synthetic decapeptides on solid phase. Eighty different decapeptides with five amino acids overlap from the human La(SS-B) autoantigen were synthesized on cellulose paper using F-moc chemistry. Tests were performed with 14 SS and six SLE sera. The results showed that the immune response to the La(SS-B) oligopeptides was restricted and unique for each individual with no particular pattern typical for each of the two diseases, apart from the fact that SLE sera gave positive reaction with fewer peptides. Regions within the N- and C-termini harboured most of the positive sequences. The authors specifically addressed the possibility of a viral aetiology for disease development or autoantibody generation. In this context the most frequently recognized linear epitopes on the La(SS-B) autoantigen showed sequence similarities with proteins from a range of ubiquitous human viruses, in particular from the herpes virus group. The La(SS-B) autoantibodies may thus be generated through molecular mimicry.

No abstract