Molecular mimicry between uveitopathogenic site of retinal S-antigen and Escherichia coli protein: induction of experimental autoimmune uveitis and lymphocyte cross-reaction.
Experimental autoimmune uveitis (EAU) is caused by the immunization of microgram amounts of a soluble retinal protein, known as S-antigen, in susceptible animal strains including primates. The disease serves as an animal model of ocular inflammation. We induced EAU and pinealitis in Lewis rats with small synthetic peptides, corresponding to the amino acid sequence in Escherichia coli protein, which contains six consecutive amino acids identical to a uveitopathogenic site in human S-antigen (peptide M). EAU and pinealitis induced in rats by synthetic peptide derived from E. coli was indistinguishable from those induced by native S-antigen or other uveitopathogenic synthetic peptides corresponding to the amino acid sequence of S-antigen. Furthermore, lymph node cells from animals immunized with either peptide M or peptide derived from E. coli protein showed significant proliferation in the presence of either peptide when tested in vitro for lymphocyte mitogenesis using [3H]thymidine. Thus, molecular mimicry, a process by which an immune response directed against a nonself protein cross-reacts with a normal host protein, may play a role in autoimmunity.
Singh
V K
VK
Molecular Biology Section, National Eye Institute, Bethesda, Maryland 20892.
Yamaki
K
K
Abe
T
T
Shinohara
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology*; D001426:Bacterial Proteins / Q000276:immunology*; D003429:Cross Reactions; D004926:Escherichia coli / Q000276:immunology*; D005136:Eye Proteins / Q000276:immunology*; D005260:Female; D008214:Lymphocytes / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D014605:Uveitis / Q000209:etiology*
D001426:Bacterial Proteins; D005136:Eye Proteins; D010446:Peptide Fragments; C052615:peptide M, retinal S antigen