MassIVE MSV000089982

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

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Description

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. [doi:10.25345/C5S46H97X] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: AAV ; Gene therapy ; Immunogenicity ; HLA class-II ; CD4 ; Adaptive immunity ; Epitope

Contact

Principal Investigators:
(in alphabetical order) 		Carlos Brito, Eli Lilly & Company, United States
Robert Siegel, Eli Lilly and Co., United States
Submitting User: cabritos

Publications

Carlos A. Brito-Sierra, Megan B. Lannan, Robert W. Siegel and Laurent P. Malherbe.
The HLA class-II immunopeptidomes of AAV capsids proteins.
Brito-Sierra CA, Lannan MB, Siegel RW and Malherbe LP (2022) The HLA class-II immunopeptidomes of AAV capsids proteins. Front. Immunol. 13:1067399. doi: 10.3389/fimmu.2022.1067399.

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