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THEMIS: Two Models, Different Thresholds.

Seeyoung Choi1, Richard Cornall2, Renaud Lesourne3

  • 1Section on Hematopoiesis and Lymphocyte Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.

Trends in Immunology
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Summary
This summary is machine-generated.

The protein THEMIS (thymus deregulation) is crucial for T cell development. New findings suggest THEMIS enhances T cell receptor (TCR) signaling, enabling thymocytes to survive positive selection.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • THEMIS (thymus deregulation) is a T-lineage-restricted protein family member.
  • Gene inactivation studies show THEMIS is essential for thymocyte positive selection.
  • THEMIS function in T cell receptor (TCR) signaling remains mechanistically unclear.

Purpose of the Study:

  • To review existing models of THEMIS function in thymocyte selection.
  • To evaluate the role of THEMIS in TCR signaling pathways.
  • To determine whether THEMIS dampens or enhances TCR signaling.

Main Methods:

  • Literature review of gene inactivation studies.
  • Analysis of data supporting different models of THEMIS function.
  • Comparative evaluation of mechanistic underpinnings.

Main Results:

  • A previous model proposed THEMIS dampens TCR signaling to prevent premature positive selection.
  • Emerging data suggest THEMIS enhances TCR signaling, facilitating thymocyte survival.
  • Evidence indicates THEMIS is necessary for thymocytes to reach the positive selection threshold.

Conclusions:

  • The preponderance of evidence supports an enhancing role for THEMIS in TCR signaling.
  • THEMIS is critical for enabling thymocytes to achieve positive selection.
  • This finding refines our understanding of T cell development and selection.