Document Detail


Molecular basis of the dual functions of 2B4 (CD244).
MedLine Citation:
PMID:  18523281     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
2B4 belongs to the CD2 family of molecules and is expressed on all NK, gammadelta, and memory CD8(+) (alphabeta) T cells. The murine NK receptor 2B4 exhibits both inhibitory and activating functions, whereas human 2B4 has been reported to be an activating molecule. How murine 2B4 can act both as an activating and inhibitory receptor and what distinguishes its function from human 2B4 have remained largely unknown. We use here a model system that allows the study of human and murine 2B4 under identical and controlled conditions. These studies reveal that both human and mouse 2B4 can activate or inhibit NK cells. We show here that the level of 2B4 expression and the degree of 2B4 cross-linking play a significant role in the regulation of signaling lymphocyte activation molecule-associated protein-mediated activation by 2B4. A high level of 2B4 expression, heavy cross-linking, and relative paucity of signaling lymphocyte activation molecule-associated protein promote inhibitory function. Our studies demonstrate how a single receptor can have opposing function depending on the degree of receptor expression, extent of its ligation, and the relative abundance of certain adaptor molecules. Because the levels of 2B4 and CD48 are dynamically regulated, these findings have implications for the regulation of NK cell function.
Authors:
Lukasz K Chlewicki; C Alejandro Velikovsky; Vamsi Balakrishnan; Roy A Mariuzza; Vinay Kumar
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  180     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-06-04     Completed Date:  2008-09-05     Revised Date:  2014-09-10    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8159-67     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Alleles
Animals
Antigens, CD / biosynthesis,  genetics,  metabolism,  physiology*
Cell Line
Humans
Hybridomas
Immunosuppressive Agents / metabolism
Intracellular Signaling Peptides and Proteins / genetics,  metabolism
Killer Cells, Lymphokine-Activated / immunology,  metabolism
Killer Cells, Natural / immunology,  metabolism
Ligands
Lymphocyte Activation / genetics,  immunology
Mice
Mice, Transgenic
Protein Binding / genetics,  immunology
Receptors, Immunologic / biosynthesis,  genetics,  metabolism,  physiology*
Grant Support
ID/Acronym/Agency:
AI 047990/AI/NIAID NIH HHS; R01 AI047990/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/CD244 protein, human; 0/CD48 antigen; 0/Cd244 protein, mouse; 0/Immunosuppressive Agents; 0/Intracellular Signaling Peptides and Proteins; 0/Ligands; 0/Receptors, Immunologic; 0/Sh2d1a protein, mouse
Comments/Corrections
Comment In:
J Immunol. 2008 Oct 15;181(8):5181; author reply 5181   [PMID:  18832667 ]

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