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Related Concept Videos

T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...

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Competitive Homing Assays to Study Gut-tropic T Cell Migration
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Optimal transport fate mapping resolves T cell differentiation dynamics across tissues.

Alec L Plotkin1,2,3, Genevieve N Mullins3,4, William D Green3,5

  • 1Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Biorxiv : the Preprint Server for Biology
|May 13, 2026
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Summary

This study introduces a new computational method to track how CD8 T cells change over time and in different tissues. It reveals distinct migration patterns and gene regulation critical for immune memory formation after viral infection.

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Area of Science:

  • Immunology
  • Computational Biology
  • Systems Biology

Background:

  • Immune cell differentiation is dynamic, involving proliferation, differentiation, and migration.
  • Static single-cell measurements hinder understanding of cell fate transitions, especially for CD8 T cells.
  • Reconstructing continuous immune cell trajectories across tissues is a significant challenge.

Purpose of the Study:

  • To develop a computational framework for reconstructing continuous CD8 T cell differentiation trajectories.
  • To map immune cell dynamics across time and multiple tissues during viral infection response.
  • To identify regulatory mechanisms governing T cell fate decisions and tissue residency.

Main Methods:

  • Optimal transport-based fate mapping framework applied to longitudinal single-cell RNA-seq data.
  • Integration of computational modeling with time-resolved in vivo labeling experiments.
  • Analysis of transcription factor regulons to identify gene regulatory programs.

Main Results:

  • Accurate recapitulation of CD8 T cell population dynamics and differentiation trajectories.
  • Identification of temporally distinct migration waves into the small intestine.
  • Discovery of CD52 as a marker for recent tissue entrants and AP4 as a regulator of cell fate specification.

Conclusions:

  • Optimal transport provides a principled framework for reconstructing immune cell fate dynamics.
  • The study provides a quantitative map of early events in antiviral CD8 T cell differentiation across tissues.
  • Findings elucidate mechanisms governing tissue-resident memory T cell formation and immunosurveillance.