Interphotoreceptor retinoid-binding protein (IRBP), a glycoprotein specific for the retina and pineal gland, induces inflammatory changes in these two organs in immunized animals. We report here on the identification of an immunodominant determinant of bovine IRBP that is highly immunogenic and immunopathogenic in the Lewis rat. The peptide, which comprises the sequence 1169-1191 of bovine IRBP, was shown to be immunodominant by its capacity to stimulate lymphocytes sensitized against whole IRBP. A comparison was made between peptide 1169-1191 and another peptide, 1158-1180, which is nondominant but is immunogenic and immunopathogenic in the Lewis rat. Peptide 1169-1191 was found to be superior in its immunological capacities; the minimal dose of 1169-1191 needed to induce cellular immune response or disease in Lewis rats (0.02-0.1 nmol/rat) is congruent to 1,000 times smaller than that of 1158-1180. In addition, unlike the ocular disease induced by 1158-1180, the disease produced by 1169-1191 resembled that induced by whole IRBP in its kinetics and histopathological features. The immunological activity of 1169-1191 in the Lewis rat was localized to the 10 residues at the COOH terminus; no such activity was exhibited by the truncated peptide 1169-1188, which comprises the 20 residues at the NH2 terminus of the full peptide. The usefulness of this unique experimental system in analyzing the role of immunodominance in peptide immunogenicity and immunopathogenicity is underscored.
Article|
June 01 1989
Identification of an immunodominant and highly immunopathogenic determinant in the retinal interphotoreceptor retinoid-binding protein (IRBP).
H Sanui,
H Sanui
Laboratory of Immunology, National Eye Institute, Bethesda, Maryland 20892.
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T M Redmond,
T M Redmond
Laboratory of Immunology, National Eye Institute, Bethesda, Maryland 20892.
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S Kotake,
S Kotake
Laboratory of Immunology, National Eye Institute, Bethesda, Maryland 20892.
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B Wiggert,
B Wiggert
Laboratory of Immunology, National Eye Institute, Bethesda, Maryland 20892.
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L H Hu,
L H Hu
Laboratory of Immunology, National Eye Institute, Bethesda, Maryland 20892.
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H Margalit,
H Margalit
Laboratory of Immunology, National Eye Institute, Bethesda, Maryland 20892.
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J A Berzofsky,
J A Berzofsky
Laboratory of Immunology, National Eye Institute, Bethesda, Maryland 20892.
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G J Chader,
G J Chader
Laboratory of Immunology, National Eye Institute, Bethesda, Maryland 20892.
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I Gery
I Gery
Laboratory of Immunology, National Eye Institute, Bethesda, Maryland 20892.
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H Sanui
Laboratory of Immunology, National Eye Institute, Bethesda, Maryland 20892.
T M Redmond
Laboratory of Immunology, National Eye Institute, Bethesda, Maryland 20892.
S Kotake
Laboratory of Immunology, National Eye Institute, Bethesda, Maryland 20892.
B Wiggert
Laboratory of Immunology, National Eye Institute, Bethesda, Maryland 20892.
L H Hu
Laboratory of Immunology, National Eye Institute, Bethesda, Maryland 20892.
H Margalit
Laboratory of Immunology, National Eye Institute, Bethesda, Maryland 20892.
J A Berzofsky
Laboratory of Immunology, National Eye Institute, Bethesda, Maryland 20892.
G J Chader
Laboratory of Immunology, National Eye Institute, Bethesda, Maryland 20892.
I Gery
Laboratory of Immunology, National Eye Institute, Bethesda, Maryland 20892.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1989) 169 (6): 1947–1960.
Citation
H Sanui, T M Redmond, S Kotake, B Wiggert, L H Hu, H Margalit, J A Berzofsky, G J Chader, I Gery; Identification of an immunodominant and highly immunopathogenic determinant in the retinal interphotoreceptor retinoid-binding protein (IRBP).. J Exp Med 1 June 1989; 169 (6): 1947–1960. doi: https://doi.org/10.1084/jem.169.6.1947
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