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Carly J. Guyver, David A. Copland, Claudia J. Calder, Alessandro Sette, John Sidney, Andrew D. Dick, Lindsay B. Nicholson; Mapping Immune Responses to mRBP-3 1-16 Peptide with Altered Peptide Ligands. Invest. Ophthalmol. Vis. Sci. 2006;47(5):2027-2035. doi: 10.1167/iovs.05-0984.
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purpose. Experimental autoimmune uveoretinitis (EAU) can be induced in C57BL/6 mice (I-Ab) using human retinoid-binding protein-3 (hRBP-3, previously IRBP) residues 1-20. This study of a truncated murine peptide (mRBP-3 1-16) was conducted to determine its pathogenic potential and to characterize partially its interaction with specific T cells.
methods. After immunization with mRBP-3 1-16 or hRBP-3 1-20, EAU was assessed by immunohistochemistry. The immune response was assessed by tritiated thymidine incorporation and cytokine production analyzed by enzyme-linked immunosorbent assay (ELISA). T-cell receptor (TCR)- and major histocompatibility complex (MHC)-binding of mRBP-3 1-16 was studied by modeling and by using altered peptide ligands (APLs) and T-cell clones.
results. mRBP-3 1-16 induced EAU in C57BL/6 mice, with severity and kinetics comparable to that after immunization with hRBP-3 1-20. T cells taken from mice immunized with mRBP-3 1-16 had a Th1 phenotype and proliferated in response to reactivation with mRBP-3 1-16, hRBP-3 1-20, or mRBP-3 1-16 APLs. mRBP-3 1-16 APLs elicited at least five distinct patterns of reactivity when tested with the mRBP-3 1-16-reactive T-cell clones.
conclusions. mRBP-3 1-16 immunizes and causes EAU in C57BL/6 mice. The studies using T-cell clones and APLs demonstrate that the immune response to mRBP-3 1-16 is drawn from a diverse population of antigen-specific T cells with a Th1 phenotype. Modeling and analysis of clones indicate that nonpathogenic T cells of an mRBP-3 1-16-reactive T-cell line recognize the peptide in a single register.
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