Antibodies to a microbial peptide sharing sequence homology with beta A(3)-crystallin damage lens epithelial cells in vitro and in vivo

Circulating auto-antibodies (Abs) against lens antigens (Ags) are highly pr evalent in patients with cataract, but their origin and pathogenic signific ance are unknown. We hypothesized that Abs raised after exposure to infecti ous microbes could cross-react with lens Ags. To test this hypothesis, we g enerated a monoclonal Ab to human beta A(3)-crystallin. Epitope analysis in dicated that the ETQAE sequence in the N-terminus region of beta A(3)-cryst allin was critical for mounting a humoral response. Similar sequences were found in three microbial Ags. Mice injected with a microbial oligopeptide c ontaining ETQAE emulsified with complete Freund's adjuvant (CFA) raised Abs which cross-reacted with beta A(3)-crystallin and developed lens epithelia l cell (LEC) damage in vitro. We also genetically engineered an beta A(3)-c rystallin-expressing E. coli, Mice immunized with the recombinant E, coli d eveloped LEC damage. These results support the hypothesis that exposure to microbes hating Ags homologous to self Ags can trigger a humoral immune res ponse that leads to LEC damage in mice.