Identification of a Novel Immunodominant HLA-B*07: 02-restricted Adenoviral Peptide Epitope and Its Potential in Adoptive Transfer Immunotherapy.
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.
*Institute for Medical Virology, University Hospital Tübingen †Department of Immunology, University of Tübingen §Pediatric Hematology/Oncology, University Children's Hospital Tübingen, Tübingen ‡Institute for Medical Microbiology, Immunology and Hygiene, Technical University Munich ∥Hematology and Oncology, Dr. von Haunersches Children's Hospital, Ludwig Maximilian University, Munich ¶German Center for Infection Research (DZIF), Tübingen and Munich, Germany.
Patrick S
PS
Günther
Janet K
JK
Peper
Benjamin
B
Faist
Simone
S
Kayser
Lena
L
Hartl
Tobias
T
Feuchtinger
Gerhard
G
Jahn
Michael
M
Neuenhahn
Dirk H
DH
Busch
Stefan
S
Stevanović
Kevin M
KM
Dennehy
D000256:Adenoviridae / Q000276:immunology*; D000257:Adenoviridae Infections / Q000276:immunology; D019264:Adoptive Transfer / Q000379:methods; D036022:Capsid Proteins / Q000276:immunology*; D045744:Cell Line, Tumor; D015793:HLA-B7 Antigen / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D016219:Immunotherapy, Adoptive / Q000379:methods; D010455:Peptides / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D036022:Capsid Proteins; C477444:HLA-B*07:02 antigen; D015793:HLA-B7 Antigen; D016056:Immunodominant Epitopes; D010455:Peptides