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CD229 (Ly9) lymphocyte cell surface receptor interacts homophilically through its N-terminal domain and relocalizes

Xavier Romero1, Nuria Zapater, María Calvo

  • 1Immunology Unit, Department of Cellular Biology and Pathology, Medical School, University of Barcelona, Spain.

Journal of Immunology (Baltimore, Md. : 1950)
|May 21, 2005
PubMed

Insights

CD229, a protein on T and B cells, acts as its own ligand, binding to itself. This homophilic interaction is crucial for its role in the immunological synapse during immune responses.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • CD229 is an Ig superfamily member expressed on T and B cells, regulating lymphocyte and NK cell functions.
  • The CD150 family, including CD229, plays roles in cytokine production and cytotoxicity.
  • CD229's cytoplasmic tail interacts with SAP, a protein linked to X-linked lymphoproliferative syndrome.

Purpose of the Study:

  • To identify the specific ligand for CD229.
  • To elucidate the mechanism of CD229-mediated cell-cell interactions.
  • To investigate CD229's role in immune synapse formation.

Main Methods:

  • Generation of a soluble CD229-Ig fusion protein to detect binding.
  • Transfection of cells with CD229 and related receptors to assess binding specificity.
  • Site-directed mutagenesis of CD229 to identify critical binding residues.
  • Confocal microscopy to analyze CD229 localization during immune synapse formation.

Main Results:

  • CD229 binds homophilically to itself, not to other CD150 family receptors.
  • The N-terminal Ig-domain of CD229 mediates this homophilic adhesion.
  • Specific mutations in charged amino acid residues compromised CD229-CD229 binding, while one mutation enhanced it.
  • CD229 relocalizes to the immune synapse between T and B cells during antigen-dependent interactions.

Conclusions:

  • CD229 functions as its own ligand, engaging in homophilic interactions.
  • These homophilic interactions are mediated by the N-terminal Ig-domain and specific amino acid residues.
  • CD229 actively participates in the formation and function of the immunological synapse.

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