دورية أكاديمية
Broadening the repertoire of melanoma-associated T-cell epitopes
| العنوان: | Broadening the repertoire of melanoma-associated T-cell epitopes |
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| المؤلفون: | Frøsig, Thomas Mørch, Lyngaa, Rikke, Met, Özcan, Larsen, Stine Kiaer, Donia, Marco, Svane, Inge Marie, Thor Straten, Per, Hadrup, Sine Reker |
| المصدر: | Frøsig , T M , Lyngaa , R , Met , Ö , Larsen , S K , Donia , M , Svane , I M , Thor Straten , P & Hadrup , S R 2015 , ' Broadening the repertoire of melanoma-associated T-cell epitopes ' , Cancer immunology, immunotherapy : CII , vol. 64 , no. 5 , pp. 609-20 . https://doi.org/10.1007/s00262-015-1664-xTest |
| سنة النشر: | 2015 |
| المجموعة: | University of Copenhagen: Research / Forskning ved Københavns Universitet |
| مصطلحات موضوعية: | Cell Line, Tumor, Epitopes, T-Lymphocyte, HLA Antigens, HLA-A1 Antigen, HLA-A11 Antigen, HLA-A3 Antigen, HLA-B7 Antigen, Humans, Immunotherapy, Adoptive, Leukocytes, Mononuclear, Lymphocytes, Tumor-Infiltrating, Melanoma, Melanoma-Specific Antigens, Peptide Mapping, T-Lymphocytes, Cytotoxic |
| الوصف: | Immune therapy has provided a significant breakthrough in the treatment of metastatic melanoma. Despite the remarkable clinical efficacy and established involvement of effector CD8 T cells, the knowledge of the exact peptide-MHC complexes recognized by T cells on the tumor cell surface is limited. Many melanoma-associated T-cell epitopes have been described, but this knowledge remains largely restricted to HLA-A2, and we lack understanding of the T-cell recognition in the context of other HLA molecules. We selected six melanoma-associated antigens (MAGE-A3, NY-ESO-1, gp100, Mart1, tyrosinase and TRP-2) that are frequently recognized in patients with the aim of identifying novel T-cell epitopes restricted to HLA-A1, -A3, -A11 and -B7. Using in silico prediction and in vitro confirmation, we identified 127 MHC ligands and analyzed the T-cell responses against these ligands via the MHC multimer-based enrichment of peripheral blood from 39 melanoma patients and 10 healthy donors. To dissect the T-cell reactivity against this large peptide library, we used combinatorial-encoded MHC multimers and observed the T-cell responses against 17 different peptide-MHC complexes in the patient group and four in the healthy donor group. We confirmed the processing and presentation of HLA-A3-restricted T-cell epitopes from tyrosinase (TQYESGSMDK) and gp100 (LIYRRRLMK) and an HLA-A11-restricted T-cell epitope from gp100 (AVGATKVPR) via the cytolytic T-cell recognition of melanoma cell lines and/or K562 cells expressing the appropriate antigen and HLA molecule. We further found T-cell reactivity against two of the identified sequences among tumor-infiltrating lymphocytes from melanoma patients, suggesting a potential clinical relevance of these sequences. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1007/s00262-015-1664-x |
| الإتاحة: | https://doi.org/10.1007/s00262-015-1664-xTest https://curis.ku.dk/portal/da/publications/broadening-the-repertoire-of-melanomaassociated-tcell-epitopesTest(080a1d4a-149e-4d47-b66d-8fa6311fd924).html |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.F44C8D2D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1007/s00262-015-1664-x |
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