Dissection of the humoral immune response toward an immunodominant epitopeof HIV: a model for the analysis of antibody diversity in HIV plus individuals

Understanding the dynamics of the humoral immune response to HIV epitopes i n the presence of genetic drift and antigenic variation of the virus may re veal critical elements of protective immunity against HIV. Analysis of anti body maturation and diversity is difficult to study at the molecular level in humans. We used a combinatorial phage display peptide library to elucida te antibody diversity in HIV-infected individuals to a single immunodominan t epitope in gp41. A serum sample derived from an HIV+ individual was used to screen a phage display a 12 mer cysteine-constrained loop peptide librar y. In doing so, we isolated mimotope-presenting phages corresponding to the immunodominant gp41 epitope CSGKLIC (residues 603-609). The mimotopes and control phages expressing epitope variants were reacted with a panel of 30 HIV+ sera. The patients showed distinct and variable recognition patterns c ompared with one another. Subfractions of the polyclonal sera were affinity purified and analyzed for epitope specificities. These analyses illustrate d that epitope variants can be used to decipher antibody diversity. Elucida tion of the plasticity of the humoral response and its polyclonality toward discrete epitopes contributes to our understanding of the antibody maturat ion process in individuals infected with viruses such as HIV.