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Functional role of human NK cell receptor 2B4 (CD244) isoforms

Stephen O Mathew1, Krithi K Rao, Jong R Kim

  • 1Department of Molecular Biology and Immunology and Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA.

European Journal of Immunology
|June 6, 2009
PubMed

Insights

Two isoforms of 2B4 (CD244), h2B4-A and h2B4-B, exhibit distinct functions in natural killer (NK) cells. h2B4-A mediates cytotoxicity and calcium release, while h2B4-B does not, suggesting differential roles in immune responses.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • 2B4 (CD244) is a molecule expressed on various immune cells, including NK cells.
  • Human NK cells express two distinct 2B4 isoforms: h2B4-A and h2B4-B, differing in their extracellular domains.

Purpose of the Study:

  • To investigate the functional differences between h2B4-A and h2B4-B isoforms.
  • To understand the impact of these isoforms on NK cell activity and CD48 binding.

Main Methods:

  • Analysis of predicted 3-D structures of h2B4 isoforms.
  • Assessing cytotoxic activity and intracellular calcium release in NK cells upon target cell recognition.
  • Evaluating the expression of h2B4 isoforms in various cell lines and primary immune cells.

Main Results:

  • h2B4-A and h2B4-B isoforms display differential binding affinities to CD48.
  • h2B4-A mediates natural cytotoxicity and calcium release against CD48-expressing cells, whereas h2B4-B does not.
  • Both isoforms are expressed in most tested cell types, with exceptions like YT and IL-2-activated NK cells lacking h2B4-B.
  • 2B4 stimulation leads to decreased mRNA levels of both isoforms, suggesting a regulatory role in NK cell activation.

Conclusions:

  • The distinct functional properties of h2B4-A and h2B4-B arise from conformational differences affecting CD48 binding.
  • Differential expression and function of 2B4 isoforms play a role in regulating NK cell-mediated immune responses.
  • Down-regulation of 2B4 isoforms is a potential mechanism for controlling NK cell activation.

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