Optimal murine CD4⁺ T cell priming by mRNA-lipid nanoparticle vaccines requires endogenous antigen processing.

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-spec

SUBMITTER: Rood JE 

PROVIDER: S-EPMC12873236 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature