Sequence homology between yeast histone H3 and uveitopathogenic site of S-antigen: lymphocyte cross-reaction and adoptive transfer of the disease.
Experimental autoimmune uveitis (EAU) serves as an animal model of ocular inflammation. The disease is caused by the immunization of microgram amounts of a soluble retinal protein, designated S-antigen, in susceptible animal strains, including primates. We induced EAU and experimental autoimmune pinealitis (EAP) in Lewis rats with a small synthetic peptide corresponding to amino acid positions 106-121 in yeast histone H3. This peptide contains five consecutive amino acids identical to a uveitopathogenic site (peptide M) in human S-antigen. Lymph node or mononuclear cells from different species of animals immunized either with histone H3 or with peptide M showed significant cross-reaction as measured by in vitro lymphocyte mitogenesis assay using [3H]thymidine. Also, we adoptively transferred the EAU and EAP in naive rats by immune lymph node cells. These findings support the fact that selected bacterial, viral, or fungal proteins with amino acid sequence homologies to normal retinal proteins are uveitopathogenic and, as such, provide a basis for autoimmune inflammatory diseases.
Singh
V K
VK
Molecular Biology Section, National Eye Institute, Bethesda, Maryland 20892.
Yamaki
K
K
Donoso
L A
LA
Shinohara
T
T
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000032:analysis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000209:etiology*; D003429:Cross Reactions; D005136:Eye Proteins / Q000032:analysis / Q000276:immunology*; D006168:Guinea Pigs; D006657:Histones / Q000032:analysis / Q000276:immunology*; D007116:Immunization, Passive; D008213:Lymphocyte Activation; D008251:Macaca; D004676:Myelin Basic Protein / Q000276:immunology; D010446:Peptide Fragments / Q000032:analysis / Q000276:immunology*; D010870:Pineal Gland; D051381:Rats; D011917:Rats, Inbred Lew; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000276:immunology*; D014605:Uveitis / Q000209:etiology* / Q000473:pathology
D000941:Antigens; D005136:Eye Proteins; D006657:Histones; D004676:Myelin Basic Protein; D010446:Peptide Fragments; C052615:peptide M, retinal S antigen