Clustering of ligand on the surface of a particle enhances adhesion to receptor-bearing cells.

Human leukocytes express a receptor that mediates the binding of cells and particles coated with C3bi, a fragment of the third component of complement. Previous data indicate that the capacity of this receptor to mediate binding is regulated by changes in its aggregation state. Randomly distributed receptors bind ligand very inefficiently, but stimulation of polymorphonuclear leukocytes with phorbol esters causes a ligand-independent clustering of the receptors in the membrane, and the clustered receptors avidly bind C3bi-coated cells (1). We examined whether the aggregation state of surface-bound ligands also affects the efficiency of binding between receptors and ligands. We found that erythrocytes bearing C3bi in clusters were bound by both macrophages and polymorphonuclear leukocytes far more avidly than erythrocytes bearing the same number of ligands in random array. We made similar observations with erythrocytes coated with C3b, a ligand that is recognized by a separate receptor. Our observations show that the ability of a receptor-bearing cell to bind particles coated with the corresponding ligands is dramatically affected by the distribution of ligand on the surface of the particle. Cell-cell interactions may thus be regulated by alterations in the two-dimensional distribution of receptors and ligands on opposing cell surfaces.