Journal article
Optimal murine CD4 + T cell priming by mRNA-lipid nanoparticle vaccines requires endogenous antigen processing
Nature communications, v 17(1), 1327
16 Jan 2026
PMID: 41545353
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines elicit robust CD4
T cell responses, yet the mechanisms underlying this T cell priming remain unknown. Antigens presented to CD4
T cells on major histocompatibility complex class II (MHC II) are traditionally acquired by antigen presenting cells (APCs) from extracellular sources. Here we show that vaccine-specific CD4
T cell responses instead rely on antigen directly expressed within APCs, without extracellular transit. Murine APCs treated with mRNA-LNP vaccines activate T cells more efficiently when presenting antigen produced internally, rather than acquired externally. Immunization with mRNA-LNP vaccines engineered to inhibit antigen expression in APCs results in lower antigen-specific CD4
T cell, T follicular helper cell, and antibody responses in mice. In contrast, excluding vaccine antigen from muscle cells minimally affects CD4
T cell responses. Our findings demonstrate that endogenous antigen presentation is essential to mRNA-LNP vaccine-induced immune responses and refine paradigms of MHC II-restricted antigen processing and presentation.
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Details
- Title
- Optimal murine CD4 + T cell priming by mRNA-lipid nanoparticle vaccines requires endogenous antigen processing
- Creators
- Julia E Rood - Children's Hospital of PhiladelphiaSuh Kyung Yoon - University of PennsylvaniaMary K Heard - Children's Hospital of PhiladelphiaStephen D Carro - University of PennsylvaniaEmma J Hedgepeth - Children's Hospital of PhiladelphiaMary E O'Mara - Children's Hospital of PhiladelphiaMichael J Hogan - Children's Hospital of PhiladelphiaNhu Le - Children's Hospital of PhiladelphiaHiromi Muramatsu - University of PennsylvaniaKieu Lam - University of British ColumbiaPetra Schreiner - University of British ColumbiaCoral Kasden - University of PennsylvaniaHansell H Stedman - University of PennsylvaniaRyan A Langlois - University of MinnesotaJames Heyes - University of British ColumbiaNorbert Pardi - University of PennsylvaniaLaurence C Eisenlohr - Children's Hospital of Philadelphia
- Publication Details
- Nature communications, v 17(1), 1327
- Publisher
- Nature Publishing
- Grant note
- R01AI153064 / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01 AI153064 / NIAID NIH HHS T32 AR076951 / NIAMS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine
- Web of Science ID
- WOS:001680374700001
- Scopus ID
- 2-s2.0-105029429475
- Other Identifier
- 991022197016004721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology