Immunological features of synthetic peptides derived from the retinal protein IRBP: differences between immunodominant and non-dominant peptides.
Interphotoreceptor retinoid-binding protein (IRBP) is a glycoprotein of 1264 residues (bovine) which localizes specifically in the retina and pineal gland and induces inflammatory changes in these organs (EAU and EAP, respectively) in immunized animals. We report here on differences between the immunological activities in Lewis rats of four IRBP-derived synthetic peptides. Only one of these peptides, designated R14 (residues: 1169-1191) is immunodominant, i.e., it has the capacity to stimulate lymphocytes sensitized against whole IRBP. The remaining peptides, R4 (1158-1180), R8 (1197-1209), and R12 (248-266), are non-dominant and are not recognized by IRBP-sensitized lymphocytes. R14 differed profoundly from the other peptides in its immunogenicity, inducing cellular immunity at the low dose of 0.1 nmol/rat, whereas the non-dominant peptides initiated immune responses at doses approximately 100 times higher. R14 was also superior to the non-dominant peptides in its antigenicity, as determined by the lowest concentration required to induce sensitized lymphocytes to proliferate. Responses were stimulated by R14 at a concentration of 10(-6) microM, while the three non-dominant peptides were stimulatory at the much higher concentration of 10(-1) microM. These data support the concept that immunodominance is linked to a high binding affinity of the peptide determinant to the major histocompatibility complex antigens on antigen-presenting cells.
Lipham
W J
WJ
National Eye Institute, NIH, Bethesda, MD 20892.
Sanui
H
H
Redmond
T M
TM
Wiggert
B
B
de Smet
M D
MD
Chader
G J
GJ
Gery
I
I
D000595:Amino Acid Sequence; D000818:Animals; D001927:Brain Diseases / Q000209:etiology; D002417:Cattle; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology; D005136:Eye Proteins; D007111:Immunity, Cellular / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology*; D010870:Pineal Gland; D051381:Rats; D011917:Rats, Inbred Lew; D012177:Retinol-Binding Proteins / Q000276:immunology*; D014605:Uveitis / Q000209:etiology; D000099214:Retinol-Binding Proteins, Interstitial
D000939:Epitopes; D005136:Eye Proteins; D010455:Peptides; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial