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Code from: A distinct antigen presentation pathway drive potent T-cell immunity in lipid nanoparticle-based mRNA vaccines

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Jun 30, 2026 version files 1.68 KB

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Abstract

In the paper by Muro et al (Science Advances 2026), to investigate whether mRNA-LNP affects the TCR repertoire of the induced CD8 T cells, we performed bulk TCR sequencing on the TCRα chains in retrogenic mice expressing a rearranged TCRβ chain. Retrogenic mice were immunized with OVA mRNA-LNP or OVA protein + poly I/C, and SIINFEKL/Kb tetramer-positive CD8 T cells were analyzed on day 14. TCR sequencing analysis showed that the number of TCR clonotypes was markedly reduced in SIINFEKL/Kb tetramer-positive CD8 T cells compared to total CD8 T cells before immunization. Principal component analysis revealed a marked similarity in the composition of OVA peptide-reactive TCRs between mice immunized with OVA mRNA-LNP and those receiving OVA protein + poly I/C. These results showed similar TCR repertoires induced by OVA mRNA-LNP and OVA + poly I/C, suggesting that the robust expansion of CD8 T cells by mRNA-LNP is primarily due to differences that are quantitative rather than qualitative compared to antigen protein and conventional adjuvants. The sequencing data have been deposited in the DDBJ Sequence Read Archive under BioProject accession number PRJDB40453.