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2B4 (CD244) is a non-MHC binding receptor with multiple functions on natural killer cells and CD8+ T cells

Megan E McNerney1, Kyung-Mi Lee, Vinay Kumar

  • 1Department of Pathology, University of Chicago, Chicago, IL 60637, USA. mcnerney@midway.uchicago.edu

Molecular Immunology
|December 21, 2004
PubMed

Insights

The 2B4 immune receptor has dual roles: it enhances T cell and natural killer (NK) cell activation through homotypic interactions but inhibits NK cell function when engaging target cells.

Area of Science:

  • Immunology
  • Cellular and Molecular Immunology

Background:

  • 2B4 (CD244) is expressed on CD8(+) T cells and natural killer (NK) cells, interacting with its ligand CD48 on hematopoietic cells.
  • Previous studies suggest 2B4 plays a role in lymphocyte activation, but its precise functions remain incompletely understood.

Purpose of the Study:

  • To elucidate the multifaceted roles of the 2B4 receptor in immune responses.
  • To investigate the mechanisms regulating 2B4's distinct signaling outcomes in T cells and NK cells.

Main Methods:

  • Utilized 2B4-deficient mice to study receptor function.
  • Employed antibody blocking strategies for in vitro and in vivo analyses.
  • Examined 2B4 interactions with CD48 on both lymphocytes and target cells.

Main Results:

  • 2B4 is crucial for optimal activation of CD8(+) T cells and NK cells via homotypic interactions with CD48 on neighboring immune cells.
  • Conversely, 2B4 engagement by CD48 on target cells inhibits NK cell effector functions.
  • Unlike typical inhibitory receptors, 2B4's inhibitory function is not regulated by MHC class I molecules.

Conclusions:

  • 2B4 exhibits context-dependent functions, acting as both an activating and inhibitory receptor.
  • Homotypic interactions involving 2B4 augment T cell and NK cell immunity.
  • The differential signaling of 2B4, independent of MHC class I, presents a unique regulatory mechanism in adaptive and innate immunity.

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