Identification of MHC Class I H-2 K<sup>b</sup>/D<sup>b</sup>-Restricted Immunogenic Peptides Derived from Retinal Proteins

Aims/hypothesis Interphotoreceptor retinoid-binding protein (IRBP) plays a major role in the visual cycle and is essential to the maintenance of photoreceptors. The aim of this study was to determine whether a decrease in IRBP production exists in the early stages of diabetic retinopathy. Methods Vitreous samples from diabetic patients with proliferative and non-proliferative diabetic retinopathy (PDR, NPDR), and from non-diabetic patients with macular hole (control group) were selected for IRBP quantitative assessment by proteomic analysis (fluorescence-based difference gel electrophoresis) and western blot. Human post mortem eyes (n=16) from diabetic donors without clinically detectable retinopathy and from non-diabetic donors (n=16) were used to determine IRBP (also known as RBP3) mRNA levels (RT-PCR) and protein content (western blot and confocal microscopy). Retinal neurodegeneration was assessed by measuring glial fibrillar acidic protein (GFAP) and the apoptotic rate. Y79 human retinoblastoma cells were used to test the effects of glucose, TNF-α and IL-1β on IRBP expression and IRBP levels. Results Intravitreous IRBP concentration was significantly lower in PDR

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“…IRBP is a dominant antigen in autoimmune uveitis [20]. Recently, moreover, proteolysis of IRBP has been shown to occur [21].…”

Section: Discussionmentioning

confidence: 99%

Interphotoreceptor retinoid-binding protein (IRBP) is downregulated at early stages of diabetic retinopathy

et al. 2009

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“…The binding activities of selected peptides to the H-2K b molecule were determined semiquantitatively by measuring peptide-induced expression of H-2K b molecules on RMA-S cells with flow cytometry. The RMA-S peptide-H-2K b stabilization assay was performed as previously described (19). Briefly, RMA-S cells were cultured at 26jC overnight and washed with serum-free medium.…”

Section: Methodsmentioning

confidence: 99%

H-2Kb–Restricted CTL Epitopes from Mouse Heparanase Elicit an Antitumor Immune Response In vivo

et al. 2008

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The identification of CTL epitopes from tumor antigens is very important for the development of peptide-based, cancerspecific immunotherapy. Heparanase is broadly expressed in various advanced tumors and can serve as a universal tumorassociated antigen. Although several epitopes of heparanase antigen are known in humans, the corresponding knowledge in mice is still rather limited. The present study was designed to predict and identify the CTL epitopes in the mouse heparanase protein. For this purpose, H-2K b -restricted CTL epitopes were identified by using the following four-step procedure: (a) a computer-based epitope prediction from the amino acid sequence of mouse heparanase, (b) a peptidebinding assay to determine the affinity of the predicted epitopes with the H-2K b molecule, (c) the testing of the induction of CTLs toward various carcinoma cells expressing heparanase antigens and H-2K b , and (d) the induction of immunoprotection and immunotherapy in vivo. The results showed that, of the tested peptides, effectors induced by peptides of mouse heparanase at residue positions 398 to 405 (LSLLFKKL; mHpa398) and 519 to 526 (FSYGFFVI; mHpa519) lysed three kinds of carcinoma cells expressing both heparanase and H-2K b (B16 melanoma cells, EL-4 lymphoma cells, and Lewis lung cancer cells). In vivo experiments indicated that mHpa398 and mHpa519 peptides offered the possibility of not only immunizing against tumors but also treating tumorbearing hosts successfully. Our results suggest that the mHpa398 and mHpa519 peptides are novel H-2K b -restricted CTL epitopes capable of inducing heparanase-specific CTLs in vitro and in vivo. These epitopes may serve as valuable tools for the preclinical evaluation of vaccination strategies. [Cancer Res 2008;68(5):1529-37]

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“…A study done by Decamps and colleagues [33] suggest that neutrophil elastase degrades the IRBP, a dominant autoantigen in autoimmune uveitis, into an immunoreactive peptide [34] which can initiate or exacerbate the immune response against IRBP and generate autoimmunity.…”

Section: Assessment Of Neutrophil Elastase Plasma Levels In Children mentioning

confidence: 99%

Clinical immunology Assessment of neutrophil elastase plasma levels in children with intermediate uveitis

Polańska¹,

Turno-Kręcicka²,

Kaźmierowska-Niemczuk³

2012

cejoi

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Identification of MHC Class I H-2 K^b/D^b-Restricted Immunogenic Peptides Derived from Retinal Proteins

Abstract: Five of 21 H-2 Kb/Db-binding retinal protein-derived peptides were found to be immunogenic, suggesting that these peptides could function as autoantigenic epitopes in the development of inflammatory eye diseases, such as uveitis.

Cited by 11 publications

References 43 publications

Interphotoreceptor retinoid-binding protein (IRBP) is downregulated at early stages of diabetic retinopathy

Interphotoreceptor retinoid-binding protein (IRBP) is downregulated at early stages of diabetic retinopathy

H-2Kb–Restricted CTL Epitopes from Mouse Heparanase Elicit an Antitumor Immune Response In vivo

Clinical immunology Assessment of neutrophil elastase plasma levels in children with intermediate uveitis

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Identification of MHC Class I H-2 Kb/Db-Restricted Immunogenic Peptides Derived from Retinal Proteins

Abstract: Five of 21 H-2 Kb/Db-binding retinal protein-derived peptides were found to be immunogenic, suggesting that these peptides could function as autoantigenic epitopes in the development of inflammatory eye diseases, such as uveitis.

Cited by 11 publications

References 43 publications

Interphotoreceptor retinoid-binding protein (IRBP) is downregulated at early stages of diabetic retinopathy

Interphotoreceptor retinoid-binding protein (IRBP) is downregulated at early stages of diabetic retinopathy

H-2Kb–Restricted CTL Epitopes from Mouse Heparanase Elicit an Antitumor Immune Response In vivo

Clinical immunology Assessment of neutrophil elastase plasma levels in children with intermediate uveitis

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Identification of MHC Class I H-2 K^b/D^b-Restricted Immunogenic Peptides Derived from Retinal Proteins