title: Identification of amino acids located in the antibody binding sites of human hepatitis A virus.
abstract: Antigenic mutants of human hepatitis A virus (human-HAV) were isolated by their resistance to neutralizing monoclonal antibodies raised to human-HAV. The nucleotide sequence determined for the capsid regions of 12 mutants identified amino acid changes that clustered in three non-overlapping sites; one in VP3 and two in VP1. All mutants had a change at amino acid residue 70 in VP3, indicating its primary importance for antibody binding. Ten mutants had two amino acid changes occurring in the VP3 site as well as one in one of the two VP1 sites. These data suggest that both sites in VP1 interact with the single VP3 site to form the immunodominant epitope of HAV. The amino acid changes found in the antigenic mutants of human-HAV selected in this study were located in the same positions as changes found in strains of HAV isolated from Old World monkeys. These simian strains of HAV are not recognized by most monoclonal antibodies raised to human-HAV, suggesting that the observed amino acid changes are part of the antibody binding site.
mesh_terms: D000596:Amino Acids / Q000276:immunology*; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D002213:Capsid / Q000276:immunology*; D036022:Capsid Proteins; D000939:Epitopes / Q000276:immunology*; D006507:Hepatovirus / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000276:immunology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D000911:Antibodies, Monoclonal; D036022:Capsid Proteins; D000939:Epitopes; D016056:Immunodominant Epitopes