LOW-AFFINITY INTERACTION OF HUMAN OR RAT T-CELL ADHESION MOLECULE CD2WITH ITS LIGAND ALIGNS ADHERING MEMBRANES TO ACHIEVE HIGH PHYSIOLOGICAL AFFINITY

The mechanism by which low affinity adhesion molecules function to pro duce stable cell-cell adhesion is unknown. In solution, the interactio n of human CD2 with its ligand CD58 is of low affinity (500 mM(-1)) an d the interaction of rat CD2 with its ligand CD48 is of still lower af finity (40 mM(-1)). At the molecular level, however, the two systems a re likely to be topologically identical. Fluorescently labeled glycosy lphosphatidylinositol-anchored CD48 and CD58 were prepared and incorpo rated into supported phospholipid bilayers, in which the ligands were capable of free lateral diffusion, Quantitative fluorescence imaging w as used to study the binding of cell surface human and rat CD2 molecul es to the fluorescent ligands in contact areas between Jurkat cells an d the bilayers. These studies provide two major conclusions. First, CD 2/ligand interactions cooperate to align membranes with nanometer prec ision leading to a physiologically effective two-dimensional affinity. This process does not require the intact cytoplasmic tail of CD2. Sec ond, the degree of membrane alignment that can be achieved by topologi cally similar receptors deteriorates with decreasing affinity. This su ggests an affinity limit for the ability of this mode of cooperativity to achieve stable cell-cell adhesion at approximately 10 mM(-1).