Identification of a potent new pathogenic site in human retinal S-antigen which induces experimental autoimmune uveoretinitis in LEW rats

Dale S. Gregerson, Carmen F. Merryman, Wesley F. Obritsch, Larry A. Donoso

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


Experimental autoimmune uveoretinitis (EAU) is a T cell-mediated autoimmune disease of the eye which can be induced in LEW rats by immunization with either human or bovine S-antigen (S-Ag). In previous reports, two nonimmunodominant pathogenic sites were found using synthetic peptides corresponding to conserved sequences at amino acid residues 303-314 and 286-297 of the bovine sequence. In this report, a 20-residue synthetic peptide encompassing amino acids 343-362 located near the C-terminus was found to be highly immunopathogenic in LEW rats. The onset of EAU was observed at as early as 8 days when high doses of a peptideencompassing residues 343-362 were used. EAU was elicited with as little as 0.5 μg of peptide per animal. Smaller peptides from this region were also tested for uveitogenicity, further refining the site to 13 amino acids. Uveitogenic T cell lines were made to this site in two ways; first, by the in vitro selection of a bulk T cell line raised to human S-Ag with peptide 343-362. Second, by the in vitro selection of a peptide-specific line from an animal immunized with peptide 352-364, which corresponds to the minimal uveitogenic site. Both of these lines adoptively transferred EAU to LEW rats, further establishing the pathogenicity of this site. A proliferative site distinct from, but overlapping, the uveitogenic site was also found. The potent uveitopathogenicity of peptides from this region indicates that it is a major pathogenic site responsible for EAU induced in LEW rats by immunization with human S-Ag.

Original languageEnglish (US)
Pages (from-to)209-219
Number of pages11
JournalCellular Immunology
Issue number1
StatePublished - Jun 1990

Bibliographical note

Funding Information:
’ This work was supported by NIH Grants EY-054 17 (D.S.G.), EY-05095 (L.A.D.), the Crippled Children’s Vitreo-Retinal Research Foundation (L.A.D.), and the Pennsylvania Lions Sight Conservation and Eye Research Foundation (L.A.D.). D.S.G. is a Research to Prevent Blindness Senior Scientific Investigator. L.A.D. is the Thomas D. Duane Professor of Ophthalmology, Jefferson Medical College, Thomas Jefferson University and is the recipient of a Manpower Award from Research to Prevent Blindness. * Abbreviations used: S-Ag, S-antigen; CB, cyanogen bromide cleaved; MBP, myelin basic protein; EAU, experimental autoimmune uveoretinitis; EAE, experimental autoimmune encephalomyelitis; BSAg, bovine S-antigen; HSAg, human S-antigen.


Dive into the research topics of 'Identification of a potent new pathogenic site in human retinal S-antigen which induces experimental autoimmune uveoretinitis in LEW rats'. Together they form a unique fingerprint.

Cite this