Human interstitial retinoid binding protein. A potent uveitopathogenic agent for the induction of experimental autoimmune uveitis.
Human interstitial retinoid binding protein (HIRBP) is a 136,000 m.w. photoreceptor cell protein which transports retinoids between the retina and the retinal pigment epithelium of the eye. The amino acid sequence of HIRBP suggests that the molecule consists of four continuous homology domains which arose by several gene duplications some 600 to 800 million years ago. When injected into susceptible animal species, including primates, it induces an experimental autoimmune uveitis (EAU), a predominantly T cell-mediated autoimmune disease of the retina and uveal tract of the eye, and the pineal gland. In order to further refine specific sites in HIRBP responsible for its uveitopathogenicity, we synthesized 120 overlapping peptide corresponding to its entire 1262 amino acid sequence, and tested each peptide for its ability to induce an EAU in Lewis rats. Five peptides with extensive amino acid sequence homology, designated HIRBP 715, HIRBP greater than 730 and HIRBP 745, HIRBP 778, and HIRBP 808 were uveitopathogenic when used at a 50 micrograms immunizing dose. The most potent peptide for the induction of EAU was HIRBP 715 (amino acid positions 521 to 540). In dose response studies as little as 0.1 microgram/animal was capable of inducing an inflammatory response. In addition, peptide HIRBP 946 which corresponds to the mid portion of peptide HIRBP 715 and contains only eight amino acids (RTATAAEE) was uveitopathogenic under our experimental conditions. Our study identifies multiple uveitopathogenic sites in HIRBP and further defines the amino acids necessary for the induction of EAU in one of these sites.
Donoso
L A
LA
Retina Service, Wills Eye Hospital, Philadelphia, PA 19107.
Merryman
C F
CF
Sery
T
T
Sanders
R
R
Vrabec
T
T
Fong
S L
SL
D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D004306:Dose-Response Relationship, Immunologic; D005136:Eye Proteins / Q000008:administration & dosage* / Q000276:immunology; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D012177:Retinol-Binding Proteins / Q000008:administration & dosage* / Q000276:immunology; D012689:Sequence Homology, Nucleic Acid; D014605:Uveitis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D000099214:Retinol-Binding Proteins, Interstitial
D005136:Eye Proteins; D010446:Peptide Fragments; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial