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Scaffolding of antigen receptors for immunogenic versus tolerogenic signaling

Jesse E Jun1, Christopher C Goodnow

  • 1Australian Cancer Research Foundation Genetics Laboratory and Medical Genome Centre, John Curtin School of Medical Research, Australian National University, Canberra ACT 2601, Australia.

Nature Immunology
|October 31, 2003
PubMed

Insights

Scaffolding proteins like CARMA1 and Cbl ubiquitin ligases dictate whether antigen receptor signaling promotes immunity or tolerance. They assemble distinct protein complexes, influencing immune responses based on various cellular factors.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • Lymphocyte antigen receptors initiate immune responses or tolerance.
  • The mechanisms encoding the polarity of antigen receptor signaling remain unclear.

Purpose of the Study:

  • To review recent findings on scaffolding molecules involved in antigen receptor signaling.
  • To elucidate how CARMA1 and Cbl proteins determine immune response polarity.

Main Methods:

  • Review of recent scientific literature.
  • Analysis of the roles of CARMA1 and Cbl ubiquitin ligases in signal complex formation.

Main Results:

  • CARMA1 and Cbl family proteins are crucial for immunogenic or tolerogenic signaling.
  • These scaffolding proteins promote the assembly of competing multiprotein complexes: immunosomes and tolerosomes.

Conclusions:

  • Scaffolding proteins integrate factors like lymphocyte differentiation and receptor engagement to influence immune polarity.
  • The balance between immunosomes and tolerosomes determines the outcome of antigen receptor signaling.

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