Experimental autoimmune uveoretinitis in mice (Biozzi ABH and NOD) expressing the autoimmune-associated H-2A(g7) molecule: identification of a uveitogenic epitope.
To determine whether Biozzi ABH (H-2A(g7)) mice were susceptible to chronic experimental autoimmune uveoretinitis (EAU). Biozzi ABH were immunized with the two retinal antigens, interphotoreceptor retinoid binding protein (IRBP) and soluble antigen (S-Ag). Biozzi ABH mice were found to be susceptible to EAU induction with native bovine IRBP. Recombinant protein domains were used to identify IRBP domain 2 (EcR2) as the uveitogenic domain. Histopathological examination indicated that EcR2-induced disease was of a chronic, non-destructive nature in the Biozzi ABH. Using synthetic overlapping peptides corresponding to EcR2, a uveitogenic and immunogenic epitope was identified corresponding to human IRBP511-530. Non-obese diabetic (NOD) mice share the same MHC class II (H-2A(g7)) molecule as the Biozzi ABH, and were also found to be susceptible to EAU induction with EcR2. This study has identified a novel mouse model of EAU, whereby disease is of a chronic, non-destructive nature, which has potential to be used in immune manipulation and neuroprotection studies.
Hankey
D J
DJ
Neuroinflammation Group, Department of Neurochemistry, Institute of Neurology, University College London, 1 Wakefield Street, WC1N 1PJ, London, UK. dhankey@hgmp.mrc.ac.uk
Nickerson
J M
JM
Donoso
L A
LA
Lightman
S L
SL
Baker
D
D
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000097:blood / Q000150:complications / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D005136:Eye Proteins; D020022:Genetic Predisposition to Disease; D006183:H-2 Antigens / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D017434:Protein Structure, Tertiary / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D012173:Retinitis / Q000097:blood / Q000150:complications / Q000276:immunology*; D012177:Retinol-Binding Proteins / Q000235:genetics / Q000276:immunology; D012720:Severity of Illness Index; D013045:Species Specificity; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014605:Uveitis / Q000097:blood / Q000150:complications / Q000276:immunology*; D000099214:Retinol-Binding Proteins, Interstitial
D001323:Autoantibodies; D000939:Epitopes; D005136:Eye Proteins; D006183:H-2 Antigens; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C108513:H-2A antigen