Type I collagen is the autoantigen in experimental autoimmune anterior uveitis.
This study was undertaken to identify and characterize the Ag responsible for the induction of experimental autoimmune anterior uveitis (EAAU). Melanin-associated Ag isolated from bovine iris and ciliary body was digested with the proteolytic enzyme V8 protease to solubilize the proteins and the pathogenic protein was purified to homogeneity. Lewis rats were sensitized to various fractions and investigated for the development of anterior uveitis and an immune response to the purified Ag. The uveitogenic Ag had a mass of 22 kDa (SDS-PAGE) and an isoelectric point of 6.75. The N-terminal amino acid sequence of this protein demonstrated 100% homology with the bovine type I collagen alpha-2 chain starting from amino acid 385 and will be referred to as CI-alpha2 (22 kDa). Animals immunized with bovine CI-alpha2 (22 kDa) developed both cellular and humoral immunity to the Ag. They developed anterior uveitis only if the CI-alpha2 chain underwent proteolysis and if the bound carbohydrates were intact. EAAU induced by CI-alpha2 (22 kDa) can be adoptively transferred to naive syngenic rats by primed CD4(+) T cells. EAAU could not be induced by the adoptive transfer of sera obtained from animals immunized with CI-alpha2 (22 kDa). The alpha-1 and alpha-2 chains (intact or proteolytically cleaved) of type I collagen from calfskin were not pathogenic. Although human anterior uveitis has been historically characterized as a collagen disease, this is first time collagen has been directly identified as the target autoantigen in uveitis.
Bora
Nalini S
NS
Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, KY 40202, USA. nsbora01@gwise.louisville.edu
Sohn
Jeong-Hyeon
JH
Kang
Shin-Goo
SG
Cruz
Jose M C
JM
Nishihori
Hiroki
H
Suk
Hye-Jung
HJ
Wang
Yali
Y
Kaplan
Henry J
HJ
Bora
Puran S
PS
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000276:immunology* / Q000302:isolation & purification; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology; D024042:Collagen Type I / Q000276:immunology*; D007106:Immune Sera / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011499:Protein Processing, Post-Translational; D051381:Rats; D011917:Rats, Inbred Lew; D014606:Uveitis, Anterior / Q000209:etiology* / Q000276:immunology
D001324:Autoantigens; D024042:Collagen Type I; D007106:Immune Sera