Journal
MATRIX BIOLOGY
Volume 28, Issue 4, Pages 202-210Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.matbio.2009.03.005
Keywords
Collagen; LAIR-1; Inhibitory receptor; Collagen Toolkit; GpVI
Categories
Funding
- Netherlands Organization for Scientific Research [016.026.008]
- Wellcome Trust
- Medical Research Council
- Medical Research Council [G0400701] Funding Source: researchfish
- MRC [G0400701] Funding Source: UKRI
Ask authors/readers for more resources
Immune responses are tightly controlled by the opposing actions of activating and inhibitory immune receptors. Previously we identified collagens as ligands for the inhibitory leukocyte-associated Ig-like receptor-1 (LAIR-1), revealing a novel mechanism of peripheral immune regulation by inhibitory immune receptors binding to extracellular matrix collagens. This interaction can be blocked by LAIR-2, a secreted member of the LAIR-1 family. LAIR-1 specifically interacts with synthetic trimeric peptides containing 10 repeats of glycine-proline-hydroxylproline (GPO) residues which can directly inhibit immune cell activation in vitro. Here we studied the interaction of human LAIR-1 and LAIR-2 with collagen in more detail by using novel overlapping synthetic trimeric peptides (Toolkits) encompassing the entire triple-helical domain of human collagens 11 and Ill. LAIR-1 and LAIR-2 bind several of these collagen-like peptides, with LAIR-2 being able to bind more than LAIR-1. LAIR binding to trimeric collagen peptides was influenced by GPO content of the peptide, although additional non-GPO triplets contributed to the interaction. Furthermore, we identified several trimeric peptides that were potent LAIR-1 ligands and could efficiently induce inhibition of T cell activation and FceRI-induced degranulation of RBL-2H3 cells through binding to LAIR-1. A detailed understanding of the LAIR recognition motifs within collagen may lead to the development of potent reagents that can be used in in vitro, ex vivo, and in vivo functional studies to dissect the biology and function of the collagen/LAIR-1 interaction. (C) 2009 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available