Abstract
Priming CD8 T cells against pathogens, tumors, and vaccinations results largely from cross-presentation of exogenous antigens by type 1 conventional dendritic cells (cDC1s). While cDC2 and monocyte-derived cells can cross-present in vitro, their physiological relevance remains unclear. Here, we used genetic models to define the distinct roles of cDC subsets in presentation of various antigen forms in vivo: tumor antigens, immune complexes, and vaccines comprised of mRNA and lipid nanoparticles (mRNA-LNP). For tumor antigen, cDC1s were necessary and sufficient to prime both CD4 and CD8 T cells. In contrast, for immune complexed antigen, either cDC1 or cDC2, but not monocyte-derived cells, could prime CD8 T cells via a shared WDFY4-dependent pathway. Notably, mRNA-LNP vaccinations elicit potent CD8 T cell responses independently of cDC1, WDFY4, and even MHC-I expression on APCs. Instead, cDC2s are a prominent component driving mRNA-LNP-mediated CD8 T cell responses and engage cross-dressing of peptide-MHC-I complexes from non-hematopoietic cells. Single cell analyses further revealed the phenotypic differences in CD8 T cells primed by cDC1 versus cDC2, suggesting their possible functional discrepancies between mRNA-LNP vaccinations and natural infections.
Committee Chair
Kenneth Murphy
Committee Members
Kodi Ravichandran; Megan Cooper; Takeshi Egawa; Wayne Yokoyama
Degree
Doctor of Philosophy (PhD)
Author's Department
Biology & Biomedical Sciences (Immunology)
Document Type
Dissertation
Date of Award
12-18-2025
Language
English (en)
DOI
https://doi.org/10.7936/0ber-w579
Author's ORCID
0000-0003-0217-4808
Recommended Citation
Jo, Suin, "Defining the Roles of cDCs in Antigen Presentation: from Tumor to mRNA Vaccines" (2025). Arts & Sciences Theses and Dissertations. 3678.
The definitive version is available at https://doi.org/10.7936/0ber-w579