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T Cell Types and Functions01:24

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Ubiquitin Specific Protease 1 Expression and Function in T Cell Immunity.

Kyla D Omilusik1, Marija S Nadjsombati2, Tomomi M Yoshida2

  • 1Division of Biological Sciences, Molecular Biology Section, University of California San Diego, La Jolla, CA agoldrath@ucsd.edu komilusik@ucsd.edu.

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The deubiquitinase USP1 regulates memory CD8+ T cell persistence and recall responses by controlling Id2 protein levels, impacting T cell immunity after reinfection.

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Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • T cells are crucial for immunity against infections and long-term protection.
  • E protein transcription factors and Id proteins regulate T cell differentiation, but their protein-level control is unclear.
  • USP1 deubiquitinase stabilizes Id2 and influences differentiation in other cell types.

Purpose of the Study:

  • Investigate the role of Usp1 in posttranslational regulation of Id2 and Id3 in mouse T cells.
  • Determine Usp1's function in T cell responses during primary and secondary infections.

Main Methods:

  • Studied Usp1 expression in activated T cells in vitro and in T cells from infected mice in vivo.
  • Analyzed Usp1 interaction with Id2 and Id3.
  • Assessed the impact of Usp1 deficiency on T cell expansion, differentiation, memory formation, and recall responses.

Main Results:

  • Usp1 expression increased upon T cell activation and correlated with T cell expansion.
  • Usp1 directly interacted with Id2 and Id3 in activated T cells.
  • Usp1 deficiency did not affect effector T cell responses during primary infection.
  • Usp1 deficiency led to memory CD8+ T cell loss and impaired recall responses upon reinfection, with reduced Id2 levels and proliferation.

Conclusions:

  • USP1 plays a role in modulating protein-level regulation of T cell recall responses, particularly affecting memory CD8+ T cell persistence.
  • Usp1 deficiency impacts T cell responses differently during primary versus secondary infections.
  • Id2/3 proteins exhibit differential regulation in immune versus non-immune cells.