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.

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 endothelial cells which line these blood vessels is a rapid process involving highly specific cellular recognition events. Although a number of lymphocyte surface molecules have been identified that mediate adhesion to high endothelial cells (the first step in extravasation), the equally important endothelial molecules which serve as their ligands are still poorly understood. By using a novel in vitro model of lymphocyte-high endothelial cell recognition, together with a series of anti-adhesive synthetic peptides, we have assessed the role of the adhesive glycoprotein fibronectin in this process. We report here that CS1, a 25-mer sequence representing the major cell recognition site within the alternatively spliced type III 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 endothelial cells. These results identify a novel ligand on high endothelial cells containing the CS1 adhesion motif (possibly a cell-surface form of fibronectin) which mediates the adhesion of lymphocytes.