Heterogeneity of human immunodeficiency virus cell-associated antigens and demonstration of virus type specificities of human antibody responses

We examined the antigens of human immunodeficiency viruses (HIV) expressed on infected H9 cells using live-cell membrane immunofluorescence and immunofluorescence absorption. Application of this nondenaturing serological method permitted analysis of HIV antigenic determinants maintained in their native configurations on the cell surface. Sera from infected individuals were found to react variably with H9 cells productively infected with nine different HIV isolates, and certain sera were completely unreactive with some isolates. Absorption of the sera prior to use in immunofluorescence revealed extensive heterogeneity of HIV cell-surface antigens and multiple type-specific antibodies in patients' sera. Immunoprecipitation and SDS-PAGE analysis of radiolabeled cell-surface proteins indicated that the predominant serological reactions were to env-encoded proteins. The observed antigenic and antibody heterogeneity likely reflects env sequence heterogeneity which has been previously reported for different HIV isolates. The demonstration of antigenic diversity among HIVs and the importance of defining the native antigenic epitopes, particularly those most widely shared, are important issues that must be considered in vaccine development.