| 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: 2008-10-21 |
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 |
Affiliation:
|
Department of Pathology, University of Chicago, Chicago, IL 60637, USA. lchlewicki@sciencetrader.com |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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 |
| 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
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Cell intrinsic TGF-beta 1 regulation of B cells.
Next Document: Tolerization of a type I allergic immune response through transplantation of genetically modified he...