Identification of a peptide inducing experimental autoimmune uveoretinitis (EAU) in H-2Ak-carrying mice.
When certain strains of mice bearing H-2Ak are immunized with the interphotoreceptor retinoid-binding protein (IRBP), EAU is induced. Thus far uveitogenic determinant(s) has not been determined in the H-2Ak mouse system. In addition it is hard to prepare purified IRBP. In the present study, to circumvent these problems we attempted to identify uveitogenic peptides derived from bovine IRBP in H-2Ak haplotype mice. Six peptides which had been selected according to the H-2Ak binding motif (Dxxxxxxxx[A, R, T]) were synthesized. We report here that all the peptides are immunogenic but only one peptide, K2, which consisted of IRBP201-216 residues, induces EAU in various mice carrying H-2Ak. Amino acid substitution of K2 revealed that the core region interacted with both H-2Ak and T cell antigen receptor (TCR). The amino acid sequence of the core region derived from bovine IRBP was identical to the corresponding region of mouse IRBP. In addition, K2 appeared to be a natural peptide antigen processed from bovine IRBP. Altogether, we concluded that K2 is one of the natural autoantigens involved in induction of EAU in H-2Ak mice.
Namba
K
K
Institute of Immunological Science, and Department of Ophthalmology, School of Medicine, Hokkaido University, Sapporo, Japan.
Ogasawara
K
K
Kitaichi
N
N
Matsuki
N
N
Takahashi
A
A
Sasamoto
Y
Y
Kotake
S
S
Matsuda
H
H
Iwabuchi
K
K
Ohno
S
S
Onoé
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology; D002417:Cattle; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology; D005136:Eye Proteins; D005260:Female; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000302:isolation & purification / Q000633:toxicity*; D010449:Peptide Mapping; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D012173:Retinitis / Q000139:chemically induced* / Q000276:immunology; D012177:Retinol-Binding Proteins / Q000276:immunology / Q000302:isolation & purification / Q000633:toxicity*; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014605:Uveitis / Q000139:chemically induced* / Q000276:immunology; D000099214:Retinol-Binding Proteins, Interstitial
D000939:Epitopes; D005136:Eye Proteins; D006183:H-2 Antigens; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C108503:antigen H-2A(k)