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Longitudinal proteomic profiling of T cell differentiation in vivo unveils dynamic proteome remodeling

This brand new study, pre-printed in BioRxiv, by Beusch et al. presents the first in vivo longitudinal proteomic profiling of antigen-specific CD8 T cells during both acute and chronic viral infections.

Using the well-established lymphocytic choriomeningitis virus (LCMV) mouse model, researchers compared the proteomes of T cells in mice infected with LCMV-Cl13 (chronic) and LCMV-Arm (acute) strains.

The study unveiled dynamic protein changes that accompany transitions between cell states, consistent with previous transcriptional and epigenetic studies. Most proteomic modulations occur during early infection stages, with more limited changes at later stages.

The research identified common proteomic modules suggesting a core T cell differentiation program and acute-specific and chronic-specific programs. The study confirmed established T cell exhaustion (TEX) markers and revealed novel proteins with potential roles in exhaustion biology. It was also shown that discrepancies between gene expression levels measured by transcriptional profiling and actual protein abundance underscoring the necessity of proteomic profiling.

This study significantly enhances our understanding of T cell differentiation and offers valuable complementary insights to other high-throughput omics approaches, potentially uncovering promising targets for drug development.

The researchers used an IonOpticks Aurora Elite CSI 15cm column for chromatographic separation. This contributed to their quantification of over 6,600 proteins across the dataset, enabling the discoveries in this critical proteomic study.


Publication
BioRxiv

Authors

Christian M. Beusch, Abdelhameed S. Dawood, Ahmet Ozdilek, Sarah Welbourn, Christopher M. Monaco, Alexandra S. Flegle, Sakshi Malik, Christina Niavi, Akil Akhtar, Carly Roman, Autumn A. Gavora, David E. Gordon, Mohamed S. Abdel-Hakeem

Title

Longitudinal proteomic profiling of T cell differentiation in vivo unveils dynamic proteome remodeling

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