MAP OF SEQUENTIAL B-CELL EPITOPES OF THE HIV-1 TRANSMEMBRANE PROTEIN USING HUMAN-ANTIBODIES AS PROBE

Antibodies of individuals infected with the human immunodeficiency virus type 1 (HIV-1) were used to probe the antigenicity of the HIV-1 transmembrane protein of 41 kD (gp41) by antibody-reactive peptide scanning (Pepscan). Eleven distinct sequential anti- body-binding sites were defined by testing reactivity to 339 overlapping nonapeptides spanning the complete gp41 amino acid sequence. Such analysis only maps continuous antibody-binding sites of nine amino acids in length and does not identify putative discontinuous or assembled epitopes. Three B cell epitopes (aa 609-622; aa 655-699; aa 664-681) at the amino-terminal border of the putative transmembrane anchor and two (aa 732-748; aa 744-762) at the carboxyl-terminal border of this domain were the most antigenic. One antibody-binding domain (aa 834-852) with four amino acids homologous to the beta-1 domain of H LA class 11 beta-chain was recognized by the serum in 1 of 4 AI DS patients tested and not by any of the eight sera from symptom-free individuals. Although functional domains of gp41 involved in virus replication, cytopathicity and possibly immunosuppression were shown to bind antibodies of HIV-l-infected individuals, no relationship between antibody recognition patterns and disease progression was apparent. © 1990 S. Karger AG, Basel.