The HLA class-II immunopeptidomes of AAV capsids proteins.
| Autor: | Brito-Sierra CA; Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, United States., Lannan MB; Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, United States., Siegel RW; Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, United States., Malherbe LP; Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, United States. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in immunology [Front Immunol] 2022 Dec 20; Vol. 13, pp. 1067399. Date of Electronic Publication: 2022 Dec 20 (Print Publication: 2022). |
| DOI: | 10.3389/fimmu.2022.1067399 |
| Abstrakt: | Introduction: Gene therapies are using Adeno-associated viruses (AAVs) as vectors, but immune responses against the capsids pose challenges to their efficiency and safety. Helper T cell recognition of capsid-derived peptides bound to human leukocyte antigen (HLA) class II molecules is an essential step in the AAV-specific adaptive immunity. Methods: Using MHC-associated peptide proteomics, we identified the HLA-DR and HLA-DQ immunopeptidomes of the capsid proteins of three different AAV serotypes (AAV2, AAV6, and AAV9) from a panel of healthy donors selected to represent a majority of allele usage. Results: The identified sequences span the capsids of all serotypes, with AAV2 having the highest peptide count. For all the serotypes, multiple promiscuous peptides were identified and displayed by both HLA-DR and -DQ. However, despite high sequence homology, there were few identical peptides among AAV2, AAV6, and AAV9 immunopeptidomes, and none were promiscuous. Discussion: 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. Competing Interests: All authors are employees and stockholders of Eli Lilly and Company. (Copyright © 2022 Brito-Sierra, Lannan, Siegel and Malherbe.) |
| Databáze: | MEDLINE |
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