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

Megan E. McNerney, Kyung Mi Lee, Vinay Kumar

Research output: Contribution to journalShort surveypeer-review

82 Citations (Scopus)


2B4 (CD244) is expressed by memory-phenotype CD8+ T cells and all natural killer (NK) cells. The ligand for 2B4, CD48, is expressed on hematopoietic cells. 2B4 is conserved in humans and mice, and a number of reports have linked 2B4 with activation of lymphocytes. We have employed 2B4-deficient mice and antibody blocking to analyze 2B4 function both in vitro and in vivo and found that 2B4 is a receptor with multiple functions. 2B4 is required for optimal activation of CD8+ T cells and NK cells - in this context 2B4 requires interaction with CD48 on neighboring lymphocytes, demonstrating that homotypic interaction within NK cell or T cell populations augments immunity. When 2B4 is engaged by CD48 on a target cell, 2B4 conversely inhibits NK effector function. As an inhibitory receptor, 2B4 is unconventional as it is not regulated by MHC class I molecules. In this review we will discuss the significance of these multiple functions and the events that may regulate differential 2B4 signaling outcome.

Original languageEnglish
Pages (from-to)489-494
Number of pages6
JournalMolecular Immunology
Issue number4 SPEC. ISS.
Publication statusPublished - 2005 Feb

Bibliographical note

Funding Information:
This work was supported by the NIH grant AI020451 (to V. Kumar) and the Medical Scientist Training Program GM07281 (to M.E. McNerney).

Copyright 2018 Elsevier B.V., All rights reserved.


  • CD150
  • CD48
  • IFNγ
  • Innate immunity
  • Tumor

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology


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