PXD040535-1
PXD040535 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | The HLA class-I immunopeptidomes of AAV capsid proteins |
| Description | Introduction: Cellular immunity is one of the main factors affecting sustained expression of gene therapies. AAV capsid-specific CD8+ T cells recognize peptides that are loaded on HLA class I molecules by cells that have been infected or transduced with AAVs. Previous studies performed by others have identified several peptides that activate CD8+ T cells, however the entire repertoire of naturally displayed peptides is unknown. Methods: Using MHC-associated peptide proteomics, we describe the HLA class I immunopeptidomes of AAV2, AAV6 and AAV9 capsids. Monocyte-derived dendritic cells (MDDCs) were isolated from a panel of 13 healthy donors that have diverse alleles representing more than 50% of the US population. MDDCs were transfected with mRNA encoding for the different AAV capsids. 6 hours post transfection, cells were lysed and peptide:HLA complexes were immunoprecipitated. Peptides were eluted and analyzed by mass spectrometry and PEAKS bioinformatic algorithms. Results: The HLA-I peptides are distributed along the entire capsids but the number of AAV9-derived peptides was significantly higher than for AAV2 or AAV6. We identified a few peptides that had been described before and are immunogenic. We also observed 14 peptides that are highly conserved among the serotypes. Finally, we observed that more than 60% of the HLA-I peptides are contained within HLA-II clusters. Discussion: This work is the first comprehensive study identifying the naturally displayed HLA class I peptides derived from the capsid of AAVs and expands on previous studies that have identified immunogenic peptides. The results from this study can be used to generate peptide pools to assess immunogenicity risk of gene therapies in the clinic. |
| HostingRepository | MassIVE |
| AnnounceDate | 2023-08-04 |
| AnnouncementXML | Submission_2023-08-04_07:55:25.195.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Carlos A. Brito-Sierra |
| SpeciesList | scientific name: Adeno-associated virus - 2; NCBI TaxID: 10804; scientific name: Adeno-associated virus - 6; NCBI TaxID: 68558; scientific name: Adeno-associated virus 9; NCBI TaxID: 235455; scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | Oxidation; Dioxidation; Cation:Na; Trp->Kynurenin; Deamidated; Dehydrated; Gln->pyro-Glu; Cysteinyl; Amidated; Glu->pyro-Glu; Acetyl; Phospho; Methyl |
| Instrument | Q Exactive HF-X |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2023-03-01 14:48:30 | ID requested | |
| ⏵ 1 | 2023-08-04 07:55:25 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: AAV, HLA class I, CD8+, Immunogenicity |
Contact List
| Carlos Brito | |
|---|---|
| contact affiliation | Eli Lilly & Company |
| contact email | carlos.brito@lilly.com |
| lab head | |
| Carlos A. Brito-Sierra | |
| contact affiliation | Eli Lilly & Company |
| contact email | carlos.brito@lilly.com |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/MSV000091389/ |
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