Antibodies to a microbial peptide sharing sequence homology with betaA3-crystallin damage lens epithelial cells in vitro and in vivo.
Circulating auto-antibodies (Abs) against lens antigens (Ags) are highly prevalent in patients with cataract, but their origin and pathogenic significance are unknown. We hypothesized that Abs raised after exposure to infectious microbes could cross-react with lens Ags. To test this hypothesis, we generated a monoclonal Ab to human betaA3-crystallin. Epitope analysis indicated that the ETQAE sequence in the N-terminus region of betaA3-crystallin was critical for mounting a humoral response. Similar sequences were found in three microbial Ags. Mice injected with a microbial oligopeptide containing ETQAE emulsified with complete Freund's adjuvant (CFA) raised Abs which cross-reacted with betaA3-crystallin and developed lens epithelial cell (LEC) damage in vitro. We also genetically engineered an betaA3-crystallin-expressing E. coli. Mice immunized with the recombinant E. coli developed LEC damage. These results support the hypothesis that exposure to microbes having Ags homologous to self Ags can trigger a humoral immune response that leads to LEC damage in mice.
Singh
D P
DP
Center for Ophthalmic Research, Brigham and Women's Hospital, The Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA.
Sueno
T
T
Kikuchi
T
T
Guru
S C
SC
Yu
S
S
Horwitz
J
J
Chylack
L T
LT
Shinohara
T
T
D000595:Amino Acid Sequence; D000818:Animals; D015551:Autoimmunity; D003429:Cross Reactions; D003459:Crystallins / Q000235:genetics / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D006801:Humans; D007114:Immunization; D007908:Lens, Crystalline / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D038205:beta-Crystallin A Chain
C489108:CRYBA1 protein, human; C051374:Cryba1 protein, mouse; D003459:Crystallins; D000939:Epitopes; D009842:Oligopeptides; D011994:Recombinant Proteins; D038205:beta-Crystallin A Chain