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Related Experiment Videos

Thyroid peroxidase as an autoantigen.

Sandra M McLachlan1, Basil Rapoport

  • 1Autoimmune Disease Unit, Cedars-Sinai Medical Center and UCLA Medical School, Los Angeles, California, USA. mclachlans@cshs.org

Thyroid : Official Journal of the American Thyroid Association
|September 8, 2007
PubMed
Summary
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Thyroid peroxidase (TPO) autoantibodies and TPO-specific T cells are key to thyroid autoimmunity. Research shows these immune responses are primarily triggered by TPO presented by thyroid cells, not damaged cells.

Area of Science:

  • Immunology
  • Endocrinology
  • Autoimmunity

Background:

  • Thyroid peroxidase (TPO) autoantibodies (TPOAbs) and TPO-specific T cells are crucial in thyroid infiltration and destruction.
  • Human monoclonal TPOAbs offer unique insights into antibody epitopes in autoimmune diseases.

Purpose of the Study:

  • To investigate the epitopes recognized by human TPOAbs and TPO-specific T cells.
  • To elucidate the role of thyroid cell presentation versus cell damage in initiating autoimmune responses against TPO.

Main Methods:

  • Characterization of human monoclonal TPOAbs and TPO-specific T cells.
  • Epitope mapping of TPO recognized by antibodies and T cells.
  • Transgenic mouse models expressing human T cell clones and intact TPO in vivo.

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Main Results:

  • Human TPOAbs target an immunodominant region (overlapping A and B domains) of intact TPO, with epitopes in MPO-homologous and CCP regions.
  • Human T cells recognize epitopes in the MPO-like region of TPO.
  • Thyrocyte processing of endogenous TPO is essential for generating T cell epitopes, and intact TPO in vivo is required for TPOAb induction in mice.

Conclusions:

  • Both TPO-specific T cells and the majority of TPOAbs in humans develop in response to TPO presented by thyroid cells.
  • This contrasts with the notion that autoimmune responses are primarily driven by TPO released from damaged thyrocytes.