Differential role for splice variants of LAIR-1 in immune cell regulation?
Thursday 5 March 2009
Prof.dr. Linde Meyaard
Project
The human leukocyte-associated immunoglobulin-like receptor (LAIR)-1 is a member of the immunoglobulin superfamily (IgSF) that is expressed on the majority of peripheral blood mononuclear cells and thymocytes. Cross-linking of LAIR-1 by monoclonal antibodies (mAb) in vitro delivers a potent inhibitory signal that is capable of inhibiting cellular functions of several immune cells.
Recently we identified collagens as ligands for LAIR-1, and observed that the collagen-LAIR-1 interaction directly inhibited immune cell function in vitro.
Splice variants of both LAIR-1 have been described: we found that LAIR-1b and LAIR-2b lack 17 amino acids in a stalk region C-terminal of the Ig-like domain compared to LAIR-1a and LAIR-2a, which may affect their glycosylation. Both isoforms of LAIR-1 are differentially expressed in a number of cell lines. LAIR-1b mediates inhibitory signals and functions similar to LAIR-1a in response to antibodies. However, we recently obtained evidence that hLAIR-1a and hLAIR-1b may differ in their capacity to respond to collagens.
In this project we will further explore the hypothesis that LAIR-1a and LAIR-1b have differential roles in immune cell inhibition and that regulation of their expression levels can be important for immune regulation.
Techniques
Cell-culture, RNA-isolations, RT-PCR, cloning, sequencing, FACS, high-speed FACS cell sorting, several immune function assays, …
Duration
6 or 9 months
Contact
Linde Meyaard, l.meyaard@umcutrecht.nl
Dr. Kristin Denzer, k.denzer@umcutrecht.nl, 088 75 576 73
More info
Website UMC Utrecht - Dept. of Immunology
References
L. Meyaard et al. (1997) LAIR-1, a novel inhibitory receptor expressed on human mononuclear leukocytes. Immunity. 7:283-90
R.J. Lebbink et al. (2004) The mouse homologue of the leukocyte-associated Ig-like receptor-1 is an inhibitory receptor that recruits Src homology region 2-containing protein tyrosine phosphatase (SHP)-2, but not SHP-1. J. Immunol. 172:5535-43
R.J. Lebbink et al. (2006) Collagens are functional, high-affinity ligands for the inhibitory immune receptor LAIR-1. J Exp Med. 203:1419-1425
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