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bioRxiv · 10.1101/2024.07.26.605251

Identification of a novel myosin antigen activating CD8+ T cells in C57BL/6 mice

Richter, L.·Bauer, M.·Bernsen, C.·Vogel, E.·Mahmud, Z.·Saliba, A.-E.·Schulz, R.·Frantz, S.·Ashour, D.·Ramos, G. C.
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Abstract

Heart-specific T cells play important roles in myocardial diseases, including myocarditis, myocardial infarction, and heart failure. However, only few cardiac antigens and their respective specific T cell receptors (TCRs) have been validated so far. Therefore, we sought to identify new cardiac T cell epitopes in C57BL/6 mice and to characterize the specific TCRs. Antigen mapping of myosin heavy chain alpha (MYHCA) led to the identification of a 9-mer epitope (MYHCA724-732) recognized by CD8+ T cells. Single-cell TCR sequencing (scTCR-seq) analysis of MYHCA-stimulated CD8+ T cells enabled the identification of distinct TCRs enriched on specific T cells. Selected TCRs inferred from scTCR-seq data were then expressed on reporter cell lines and functionally validated. Our study expands the toolkit required to study heart-directed immune responses by revealing a new cardiac antigen and specific TCRs. These tools will enable in vivo characterization of myosin-specific CD8+ T cells in murine models of myocardial diseases.

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Richter, L., Bauer, M., Bernsen, C., Vogel, E., Mahmud, Z., Saliba, A.-E., Schulz, R., Frantz, S., Ashour, D., Ramos, G. C.. 2024-07-26. Identification of a novel myosin antigen activating CD8+ T cells in C57BL/6 mice. https://doi.org/10.1101/2024.07.26.605251

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