Analysis of the uveitogenic determinant in repeat structure of retinal interphotoreceptor retinoid-binding protein (IRBP).
IRBP is a glycolipoprotein with a four-fold partially homologous repeat structure approximately 300 residues in length, and is one of the retinal antigens capable of inducing experimental autoimmune uveoretinitis (EAU) in susceptible animals by their active immunization. The most immunopathogenic peptide of bovine IRBP for EAU in Lewis rats is reported to be the sequence 1169-1191 (PTARSVGAADGSSWEGVGVVPDV) with two immunogenic motifs common to T cell epitopes (underlined). The uveitogenic site of peptide 1169-1191 was localized at the carboxyl terminus (peptide 1182-1191) and not at the amino acid terminus (peptide 1169-1182). Repeat peptides of sequence 1179-1191 containing the four homologous residues (1182W, 1186G, 1187V and 1189P), that is the peptides 271-283, 579-591 and 880-892, all elicited EAU. Peptide 579-591 could not stimulate proliferation of lymphocytes from rats immunized with IRBP, but had the capacity to adoptively transfer EAU. The role of the homologous residues was examined using analogues of the uveitogenic peptide 1182-1194, in which each homologous residue was substituted by glycine (G) or leucine (L) (1182W-->G, 1186G-->L, 1187V-->G, and 1189P-->G). One analogue (1186G-->L) strongly diminished the ability to induce EAU, while the other three analogues completely abolished the ability, indicating that these homologous residues were essential for the induction of EAU. In addition, the uveitogenic peptides tested in this study were found not to contain the major epitope for antibody production.
Inoue
H
H
Department of Ophthalmology, Tokyo Medical College Hospital, Japan.
Takeuchi
M
M
Tanaka
T
T
Usui
M
M
Ando
S
S
Taguchi
O
O
D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D005136:Eye Proteins; D017710:Lymphocyte Transfusion; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D012177:Retinol-Binding Proteins / Q000737:chemistry* / Q000276:immunology; D014605:Uveitis / Q000276:immunology*; D014611:Vaccination; D000099214:Retinol-Binding Proteins, Interstitial
D005136:Eye Proteins; D010446:Peptide Fragments; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial