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Related Experiment Videos

T cells with two functional antigen-specific receptors

F Hardardottir1, J L Baron, C A Janeway

  • 1Section of Immunobiology, Yale University School of Medicine, New Haven, CT.

Proceedings of the National Academy of Sciences of the United States of America
|January 17, 1995
PubMed
Summary
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Some T cells express two T-cell receptors (TCRs), each recognizing a different antigen-MHC complex. However, typically only one TCR specificity is functional for self-MHC recognition, influencing autoimmune disease susceptibility.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • The clonal selection theory posits lymphocytes have single-specificity receptors.
  • Evidence suggests some T cells express dual-specificity receptors.
  • T-cell receptor (TCR) function is central to adaptive immunity.

Purpose of the Study:

  • To investigate the specificity of T cells expressing two functional TCRs.
  • To understand the implications of dual TCR expression in autoimmune disease.
  • To examine TCR expression in transgenic mouse models.

Main Methods:

  • Utilized mice engineered with genes for an autoreactive T-cell receptor (TCR).
  • Analyzed T cell development and TCR expression in different major histocompatibility complex (MHC) environments.

Related Experiment Videos

  • Assessed T cell specificity in relation to MHC molecules.

    • Main Results:

    • T cells in mice lacking the self-MHC recognized by the transgene-encoded TCR expressed both TCRs.
    • These dual-TCR T cells recognized distinct antigen-MHC complexes.
    • T cells developed in the presence of the specific MHC predominantly expressed the transgene-encoded TCR.
    • Mice lacking self-MHC tolerance were susceptible to autoimmune disease.

    Conclusions:

    • Most dual-TCR T cells possess only one TCR specific for self-MHC peptides.
    • Dual TCR expression typically does not confer reactivity to two unrelated antigens.
    • TCR specificity and MHC interaction are critical in T cell development and autoimmunity.