A consensus pool of T-cell epitopes from adenoviral antigens

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dc.contributor.advisor Stevanović, Stefan (Prof. Dr.)
dc.contributor.author März, Léo
dc.date.accessioned 2022-06-10T10:05:21Z
dc.date.available 2022-06-10T10:05:21Z
dc.date.issued 2022-06-10
dc.identifier.uri http://hdl.handle.net/10900/128015
dc.identifier.uri http://nbn-resolving.de/urn:nbn:de:bsz:21-dspace-1280152 de_DE
dc.identifier.uri http://dx.doi.org/10.15496/publikation-69378
dc.description.abstract In immunocompromised patients, an adenoviral infection can turn into a fulminant progression of the disease, which often leads to death. Adoptive T-cell transfer was identified as a promising treatment approach. For the selection of virus-specific T cells, the knowledge of immunodominant epitopes is required. Within the scope of this project, HAdV-derived epitopes were identified and further investigated. We aimed to design one HLA class I and one HLA class II epitope cocktail that should lead to an immune response in ELISpot assays with randomly selected PBMC cultures. We compared the immune response to two HLA class I cocktails: one contained 24 HLA class I epitopes and the other contained the 15 epitopes with the highest recognition rates. The 24-peptides-cocktail elicited a IFN-γ response in 22 out of 25 PBMC cultures (88%). The 15 peptides cocktail led to a detectable IFN-γ response in 20 out of 25 PBMC cultures (80%). The 24-peptides-cocktail was always able to stimulate the PBMCs of donors, which were responsive to the 15 peptides cocktail. To date, there is no satisfying tool for promiscuous HLA class II epitope prediction. We performed a promiscuous epitope prediction on all 46 reviewed HAdV2 proteins from the Swiss-Prot database with SYFPEITHI and NetMHCIIpan 2.0. The top-ranked peptides and already published epitopes were synthesized and screened for immunogenicity in ELISpot assays. We designed an HLA class II peptide cocktail containing the 12 most immunogenic epitopes, proven to stimulate CD4+ T cells via ICS. Four epitopes are already published, seven of the epitopes were first identified by our prediction, and one epitope is an elongated HLA class I 10mer showing CD4+ T cell stimulation in ICS. The designed HLA class II cocktail could stimulate 31 out of 31 tested PBMC cultures (100%) in ELISpot assays. The assumption that the hexon protein is the main target of the immune response can be questioned as seven immunodominant HLA class II epitopes newly-discovered by the promiscuous prediction are derived from other proteins than the hexon. We identified an effective method for the prediction of promiscuous HLA class II epitopes. The combined SYFPEITHI/ NetMHCIIpan 2.0 prediction resulted in the synthesis of 27 peptides, from which nine (33.3%) were identified as immunodominant and twelve (44.4%) were categorized as subdominant epitopes. One of the dominant epitopes is already published. Six peptides (22.2%) were non-immunogenic. One immunodominant epitope was revealed as an HLA class I epitope in ICS. en
dc.language.iso en de_DE
dc.publisher Universität Tübingen de_DE
dc.rights ubt-podok de_DE
dc.rights.uri http://tobias-lib.uni-tuebingen.de/doku/lic_mit_pod.php?la=de de_DE
dc.rights.uri http://tobias-lib.uni-tuebingen.de/doku/lic_mit_pod.php?la=en en
dc.subject.ddc 500 de_DE
dc.subject.ddc 570 de_DE
dc.subject.ddc 610 de_DE
dc.subject.other HAdV (human adenovirus) en
dc.subject.other HLA class II epitopes en
dc.subject.other HLA class I epitopes en
dc.subject.other peptide pools en
dc.subject.other antiviral T cells en
dc.subject.other epitope prediction en
dc.subject.other promiscuous CD4+ T-cell epitopes en
dc.title A consensus pool of T-cell epitopes from adenoviral antigens en
dc.type Dissertation de_DE
dcterms.dateAccepted 2022-05-10
utue.publikation.fachbereich Medizin de_DE
utue.publikation.fakultaet 4 Medizinische Fakultät de_DE
utue.publikation.noppn yes de_DE


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