Identification of a Novel Immunodominant HLA-B*07: 02-restricted Adenoviral Peptide Epitope and Its Potential in Adoptive Transfer Immunotherapy
| Autor: | Tobias Feuchtinger, Simone Kayser, Lena Hartl, Benjamin Faist, Stefan Stevanovic, Kevin M. Dennehy, Michael Neuenhahn, Patrick Günther, Gerhard Jahn, Janet Kerstin Peper, Dirk Büsch |
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| Rok vydání: | 2015 |
| Předmět: |
Cancer Research
Adoptive cell transfer medicine.medical_treatment Adenoviridae Infections T-Lymphocytes Immunology Human leukocyte antigen Biology Immunotherapy Adoptive Epitope Adenoviridae HLA-B7 Antigen Cell Line Tumor medicine Immunology and Allergy Cytotoxic T cell Humans Adenovirus infection Hexon protein Pharmacology Immunodominant Epitopes Immunotherapy medicine.disease Virology Adoptive Transfer Capsid Proteins Peptides Ex vivo |
| Zdroj: | Journal of immunotherapy (Hagerstown, Md. : 1997). 38(7) |
| ISSN: | 1537-4513 |
| Popis: | Adenovirus infections of immunocompromised patients, particularly following allogeneic hematopoietic stem cell transplantation, are associated with morbidity and mortality. Immunotherapy by adoptive transfer of hexon-specific and penton-specific T cells has been successfully applied, but many approaches are impeded by the low number of HLA class I-restricted adenoviral peptide epitopes described to date. We use a novel method to identify naturally presented adenoviral peptide epitopes from infected human cells, ectopically expressing defined HLA, using peptide elution and liquid chromatography-mass spectrometry analysis. We show that the previously described HLA-A*01:01-restricted peptide epitope LTDLGQNLLY from hexon protein is naturally presented, and demonstrate the functionality of LTDLGQNLLY-specific T cells. We further identify a novel immunodominant HLA-B*07:02-restricted peptide epitope VPATGRTLVL from protein 13.6 K, and demonstrate the high proliferative, cytotoxic, and IFN-γ-producing capacity of peptide-specific T cells. Lastly, LTDLGQNLLY-specific T cells can be detected ex vivo following adoptive transfer therapy, and LTDLGQNLLY-specific and VPATGRTLVL-specific T cells have memory phenotypes ex vivo. Given their proliferative and cytotoxic capacity, such epitope-specific T cells are promising candidates for adoptive T-cell transfer therapy of adenovirus infection. |
| Databáze: | OpenAIRE |
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