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The HLA class-II immunopeptidome of AAV2, AAV6 and AAV9 capsid proteins

ABSTRACT: Peptides bound to the human leukocyte antigen (HLA) class-II represent potential epitopes responsible for initiating an adaptive immune response to Adeno-associated viruses (AAVs). We dosed monocyte-derived dendritic (moDCs) cells with capsid protein of AAV2, AAV6, or AAV9 serotypes. The moDCs were isolated from ten donors covering more than 60% allele frequency in the country. Using mass spectrometry, we identified peptide sequences encompassing the entire capsid protein, and several peptides are displayed among multiple donors, suggesting the promiscuity of binding. Noteworthy, multiple highly promiscuous peptides were displayed in both HLA-DR and -DQ receptors. Our data also highlights a panel of conserved peptides among serotypes that are predominantly restricted to a few donors. Results from this work represent a comprehensive immunopeptidomics research of potential CD4+ T cell epitopes and provide the basis for immunosurveillance efforts for safer and more efficient AAV-based gene therapies.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Adeno-associated Virus - 6 (ncbitaxon:68558) Adeno-associated Virus 9 (ncbitaxon:235455) Adeno-associated Virus - 2 (ncbitaxon:10804)

SUBMITTER: Carlos Brito Robert Siegel

PROVIDER: MSV000089982 | MassIVE | Tue Jul 26 12:29:00 BST 2022

REPOSITORIES: MassIVE

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