Characterization of the interaction between human LAIR-1 and collagens. (101.8)

Abstract

Abstract Human leukocyte-associated Ig-like receptor-1 (LAIR-1) is an immunoreceptor tyrosine based inhibitory motif (ITIM) containing inhibitory receptor that is expressed on the majority of PBMCs and thymocytes. The ligand for LAIR-1 has recently been identified as collagens. Since collagens represent the most abundant type of proteins in vertebrates it is reasonable to think that LAIR-1 could have a very important role in controlling many aspects of the immune response. To study the interaction of LAIR-1 with collagens, we use a reporter cell system expressing a chimeric receptor composed of the extracellular domain of LAIR-1 and the transmembrane and cytoplasmic domains of the CD3æ chain. Using this reporter system we have found that both purified collagens type I and type IV are ligands for LAIR-1. Moreover, we have also found that LAIR-1 can interact with collagen type IV that is present in the extracellular matrix and basement membranes. In addition, we have identified a pivotal residue in the extracellular domain of LAIR-1 that could be required for a functional interaction with collagens type I and type IV. Then, by confocal microscopy, we have observed the accumulation and polarization of LAIR-1-EGFP at the binding sites with collagens type I and IV and matrigel. This polarization is very fast and dynamic in nature. An analysis of the role of ITIM motifs in the interaction of LAIR-1 with collagens will be discussed.