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Inhibition and activation by CD244 depends on CD2 and phospholipase C-gamma1

Nicholas G Clarkson1, Marion H Brown

  • 1Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom.

The Journal of Biological Chemistry
|July 10, 2009
PubMed

Insights

The CD244 receptor

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • CD244 is a cell surface receptor on NK and T cells, crucial for immune responses.
  • Its regulation involves cell surface interactions with CD48 and intracellular partners like SAP and EAT-2.
  • Mouse models present challenges due to CD2 also binding CD48, complicating CD244 studies.

Purpose of the Study:

  • To differentiate the roles of mouse CD244 and CD2 in CD48 engagement.
  • To elucidate the distinct signaling pathways of CD244 in humans and mice.
  • To identify novel signaling mechanisms for CD244, particularly through the EAT-2 adaptor protein.

Main Methods:

  • Utilized a mouse T cell hybridoma model to study CD244 and CD2 interactions with CD48.
  • Investigated the impact of mutations in proline-rich and tyrosine motifs of CD2 and CD244 on immune response.
  • Employed biochemical assays to explore intracellular interactions and signaling pathways.

Main Results:

  • Both CD2 and CD244 positively contribute to immune responses, evidenced by reduced interleukin-2 production upon mutation.
  • Mouse CD244's inhibitory effects are explained by competition with CD2 for CD48 binding.
  • Identified a novel CD244 signaling pathway involving recruitment of phospholipase C-gamma1 via EAT-2.

Conclusions:

  • CD244 and CD2 signaling pathways are distinct yet interconnected, with implications for immune regulation.
  • Mouse CD244 function is modulated by competition with CD2 for CD48.
  • A conserved intracellular link between CD2 and CD244, potentially via FYN kinase, exists in humans, and CD244 signaling through EAT-2 is critical for its function.

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