Sec22b and Stx4 Depletion Has No Major Effect on Cross-Presentation of PLGA Microsphere-Encapsulated Antigen and a Synthetic Long Peptide In Vitro.
Journal
Journal of immunology (Baltimore, Md. : 1950)
ISSN: 1550-6606
Titre abrégé: J Immunol
Pays: United States
ID NLM: 2985117R
Informations de publication
Date de publication:
15 10 2023
15 10 2023
Historique:
received:
29
06
2022
accepted:
08
08
2023
pmc-release:
15
10
2024
medline:
4
10
2023
pubmed:
28
8
2023
entrez:
28
8
2023
Statut:
ppublish
Résumé
The induction of CTL responses by vaccines is important to combat infectious diseases and cancer. Biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres and synthetic long peptides are efficiently internalized by professional APCs and prime CTL responses after cross-presentation of Ags on MHC class I molecules. Specifically, they mainly use the cytosolic pathway of cross-presentation that requires endosomal escape, proteasomal processing, and subsequent MHC class I loading of Ags in the endoplasmic reticulum (ER) and/or the endosome. The vesicle SNARE protein Sec22b has been described as important for this pathway by mediating vesical trafficking for the delivery of ER-derived proteins to the endosome. As this function has also been challenged, we investigated the role of Sec22b in cross-presentation of the PLGA microsphere-encapsulated model Ag OVA and a related synthetic long peptide. Using CRISPR/Cas9-mediated genome editing, we generated Sec22b knockouts in two murine C57BL/6-derived APC lines and found no evidence for an essential role of Sec22b. Although pending experimental evidence, the target SNARE protein syntaxin 4 (Stx4) has been suggested to promote cross-presentation by interacting with Sec22b for the fusion of ER-derived vesicles with the endosome. In the current study, we show that, similar to Sec22b, Stx4 knockout in murine APCs had very limited effects on cross-presentation under the conditions tested. This study contributes to characterizing cross-presentation of two promising Ag delivery systems and adds to the discussion about the role of Sec22b/Stx4 in related pathways. Our data point toward SNARE protein redundancy in the cytosolic pathway of cross-presentation.
Identifiants
pubmed: 37638825
pii: 265879
doi: 10.4049/jimmunol.2200473
pmc: PMC10592162
mid: NIHMS1924434
doi:
Substances chimiques
Antigens
0
Peptides
0
Qa-SNARE Proteins
0
R-SNARE Proteins
0
Sec22b protein, mouse
0
Stx4a protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1203-1215Subventions
Organisme : NCI NIH HHS
ID : R21 CA274064
Pays : United States
Informations de copyright
Copyright © 2023 by The American Association of Immunologists, Inc.
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