Identification of Candidate Tolerogenic CD8+ T Cell Epitopes for Therapy of Type 1 Diabetes in the NOD Mouse Model
Type 1 diabetes is an autoimmune disease in which insulin-producing pancreatic islet β cells are the target of self-reactive B and T cells. T cells reactive with epitopes derived from insulin and/or IGRP are critical for the initiation and maintenance of disease, but T cells reactive with other isle...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2016/9083103 |
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| author | Cailin Yu Jeremy C. Burns William H. Robinson Paul J. Utz Peggy P. Ho Lawrence Steinman Alan B. Frey |
| author_facet | Cailin Yu Jeremy C. Burns William H. Robinson Paul J. Utz Peggy P. Ho Lawrence Steinman Alan B. Frey |
| author_sort | Cailin Yu |
| collection | DOAJ |
| description | Type 1 diabetes is an autoimmune disease in which insulin-producing pancreatic islet β cells are the target of self-reactive B and T cells. T cells reactive with epitopes derived from insulin and/or IGRP are critical for the initiation and maintenance of disease, but T cells reactive with other islet antigens likely have an essential role in disease progression. We sought to identify candidate CD8+ T cell epitopes that are pathogenic in type 1 diabetes. Proteins that elicit autoantibodies in human type 1 diabetes were analyzed by predictive algorithms for candidate epitopes. Using several different tolerizing regimes using synthetic peptides, two new predicted tolerogenic CD8+ T cell epitopes were identified in the murine homolog of the major human islet autoantigen zinc transporter ZnT8 (aa 158–166 and 282–290) and one in a non-β cell protein, dopamine β-hydroxylase (aa 233–241). Tolerizing vaccination of NOD mice with a cDNA plasmid expressing full-length proinsulin prevented diabetes, whereas plasmids encoding ZnT8 and DβH did not. However, tolerizing vaccination of NOD mice with the proinsulin plasmid in combination with plasmids expressing ZnT8 and DβH decreased insulitis and enhanced prevention of disease compared to vaccination with the plasmid encoding proinsulin alone. |
| format | Article |
| id | doaj-art-5a4a980daeee4972aa73e3daa632d723 |
| institution | OA Journals |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-5a4a980daeee4972aa73e3daa632d7232025-08-20T02:05:28ZengWileyJournal of Diabetes Research2314-67452314-67532016-01-01201610.1155/2016/90831039083103Identification of Candidate Tolerogenic CD8+ T Cell Epitopes for Therapy of Type 1 Diabetes in the NOD Mouse ModelCailin Yu0Jeremy C. Burns1William H. Robinson2Paul J. Utz3Peggy P. Ho4Lawrence Steinman5Alan B. Frey6Department of Cell Biology, New York University Langone School of Medicine, 550 First Avenue, New York, NY 10016, USADepartment of Cell Biology, New York University Langone School of Medicine, 550 First Avenue, New York, NY 10016, USADivision of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USADivision of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USADepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USADepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USADepartment of Cell Biology, New York University Langone School of Medicine, 550 First Avenue, New York, NY 10016, USAType 1 diabetes is an autoimmune disease in which insulin-producing pancreatic islet β cells are the target of self-reactive B and T cells. T cells reactive with epitopes derived from insulin and/or IGRP are critical for the initiation and maintenance of disease, but T cells reactive with other islet antigens likely have an essential role in disease progression. We sought to identify candidate CD8+ T cell epitopes that are pathogenic in type 1 diabetes. Proteins that elicit autoantibodies in human type 1 diabetes were analyzed by predictive algorithms for candidate epitopes. Using several different tolerizing regimes using synthetic peptides, two new predicted tolerogenic CD8+ T cell epitopes were identified in the murine homolog of the major human islet autoantigen zinc transporter ZnT8 (aa 158–166 and 282–290) and one in a non-β cell protein, dopamine β-hydroxylase (aa 233–241). Tolerizing vaccination of NOD mice with a cDNA plasmid expressing full-length proinsulin prevented diabetes, whereas plasmids encoding ZnT8 and DβH did not. However, tolerizing vaccination of NOD mice with the proinsulin plasmid in combination with plasmids expressing ZnT8 and DβH decreased insulitis and enhanced prevention of disease compared to vaccination with the plasmid encoding proinsulin alone.http://dx.doi.org/10.1155/2016/9083103 |
| spellingShingle | Cailin Yu Jeremy C. Burns William H. Robinson Paul J. Utz Peggy P. Ho Lawrence Steinman Alan B. Frey Identification of Candidate Tolerogenic CD8+ T Cell Epitopes for Therapy of Type 1 Diabetes in the NOD Mouse Model Journal of Diabetes Research |
| title | Identification of Candidate Tolerogenic CD8+ T Cell Epitopes for Therapy of Type 1 Diabetes in the NOD Mouse Model |
| title_full | Identification of Candidate Tolerogenic CD8+ T Cell Epitopes for Therapy of Type 1 Diabetes in the NOD Mouse Model |
| title_fullStr | Identification of Candidate Tolerogenic CD8+ T Cell Epitopes for Therapy of Type 1 Diabetes in the NOD Mouse Model |
| title_full_unstemmed | Identification of Candidate Tolerogenic CD8+ T Cell Epitopes for Therapy of Type 1 Diabetes in the NOD Mouse Model |
| title_short | Identification of Candidate Tolerogenic CD8+ T Cell Epitopes for Therapy of Type 1 Diabetes in the NOD Mouse Model |
| title_sort | identification of candidate tolerogenic cd8 t cell epitopes for therapy of type 1 diabetes in the nod mouse model |
| url | http://dx.doi.org/10.1155/2016/9083103 |
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