Use of synthetic peptides to probe lymphocyte- high endothelial cell interactions. Lymphocytes recognize a ligand on the endothelial surface which contains the CS1 adhesion motif

Abstract

The extravasation of recirculating lymphocytes into lymph nodes, which is crucial for immune system function, occurs constitutively from specialized post-capillary venules in the lymph node paracortex. The migration of lymphocytes between the structurally distinct high endotheiial cells which line these blood vessels is a rapid process involving highly specttic cellular recognition events. Although a number of lymphocyte surface molecules have been Identified that mediate adhesion to high endotheiiai cells (the first step in extravasation), the equally important endotheiiai molecules which serve as their iigands are still poorly understood. By using a novel in vitro model of lymphocyte - high endotheliai cell recognition, together wlth a series of antiadhesive synthetic peptides, we have assessed the role of the adhesive giycoprotein fibronectin in this process. We report here that CS1, a 25-mer sequence representing the major cell recognition site within the alternatively spliced type ill connecting segment of fibronectin, supports the adhesion of rat lymphocytes and that it is a specific inhibitor of lymphocyte adhesion to the surface of high endotheiial cells. These results identify a novel ligand on high endotheiiai cells containing the CS1 adhesion mottf (possibly a cell-surface form of fibronectin) which mediates the adhesion of lymphocytes.