Functional requirements for inhibitory signal transmission by the immunomodulatory receptor CD300a

BMC Immunology

Research Article

Venkateswara R Simhadri¹  Francisco Borrego¹  John L Mariano¹  Karen E DeBell¹ 

[1] Division of Monoclonal Antibodies HFD-123, Laboratory of Molecular and Developmental Immunology, OBP/CDER/FDA, 29 Lincoln Drive; Bldg 29B, Room 3NN18, 20892, Bethesda, MD, USA;

关键词: Tyrosine Phosphorylation;    Chimeric Receptor;    CD300a Expression;    Intracellular Tail;    Pervanadate Treatment;   

DOI  :  10.1186/1471-2172-13-23

 received in 2011-11-09, accepted in 2012-04-26,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundActivation signals can be negatively regulated by cell surface receptors bearing immunoreceptor tyrosine-based inhibitory motifs (ITIMs). CD300a, an ITIM bearing type I transmembrane protein, is expressed on many hematopoietic cells, including subsets of lymphocytes.ResultsWe have taken two approaches to further define the mechanism by which CD300a acts as an inhibitor of immune cell receptor signaling. First, we have expressed in Jurkat T cells a chimeric receptor consisting of the extracellular domains of killer-cell immunoglobulin-like receptor (KIR)2DL2 fused to the transmembrane and cytoplasmic segments of CD300a (KIR-CD300a) to explore surrogate ligand-stimulated inhibition of superantigen stimulated T cell receptor (TCR) mediated cell signaling. We found that intact CD300a ITIMs were essential for inhibition and that the tyrosine phosphorylation of these ITIMs required the src tyrosine kinase Lck. Tyrosine phosphorylation of the CD300a ITIMs created docking sites for both src homology 2 domain containing protein tyrosine phosphatase (SHP)-1 and SHP-2. Suppression of SHP-1 and SHP-2 expression in KIR-CD300a Jurkat T cells with siRNA and the use of DT40 chicken B cell lines expressing CD300a and deficient in several phosphatases revealed that SHP-1, but not SHP-2 or the src homology 2 domain containing inositol 5’ phosphatase SHIP, was utilized by CD300a for its inhibitory activity.ConclusionThese studies provide new insights into the function of CD300a in tuning T and B cell responses.

【 授权许可】

Unknown   
© DeBell et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.