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Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
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Germline T cell receptor exchange results in physiological T cell development and function.

Meagan R Rollins1,2, Jackson F Raynor1,2, Ebony A Miller1,2

  • 1Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USA.

Nature Communications
|February 1, 2023
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We developed T cell receptor exchange (TRex) mice for studying antigen-specific immunity. TRex mice enable physiologic T cell development and behavior analysis, advancing immunology research.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • T cell receptor (TCR) transgenic mice are crucial for studying immune responses.
  • Existing models use non-physiologic promoters and random genome integration.
  • This limits the study of natural T cell behavior.

Purpose of the Study:

  • To develop an efficient methodology for creating T cell receptor exchange (TRex) mice.
  • To enable physiologic T cell development and antigen-specific immune response studies.
  • To investigate T cell tolerance and functional sensitivity.

Main Methods:

  • Created TRex mice integrating TCRs into the Trac locus.
  • Disrupted the mesothelin (Msln) gene to circumvent T cell tolerance.
  • Compared TCRs with varying affinities and generated P14 TRex mice.

Main Results:

  • TRex thymocytes exhibited normal maturation and TCR expression.
  • T cell tolerance was overcome by Msln disruption.
  • Trac targeting enhanced TCR functional sensitivity and avidity.
  • Physiologic T cell development was preserved.

Conclusions:

  • The TRex methodology provides an advanced tool for studying physiological antigen-specific T cell behavior.
  • TRex mice overcome limitations of traditional transgenic models.
  • This approach facilitates deeper understanding of T cell responses.