MAKING A LITTLE AFFINITY GO A LONG WAY - A TOPOLOGICAL VIEW OF LFA-1 REGULATION

Lymphocytes utilize adhesion to navigate in the body and to transientl y interact with a variety of potential antigen presenting cells. Inter actions of adhesion molecules are governed by the law of mass action a nd the less understood rules of apposed biological membranes. Biochemi cal parameters such as adhesion molecule affinity only tell part of th e story. Factors such as lateral mobility, membrane alignment and cyto skeletal interactions are equally important in determining the final o utcome. Therefore it is important to determine mechanisms by which the properties of cell membranes and the cytoskeleton reinforce or hinder adhesion molecule interactions. Work from my lab has shown that one m echanism by which lymphocyte adhesion molecules cooperate is to align adhering membranes with nanometer precision. Here, I discuss a model f or LFA-I regulation that is dependent on three independent processes: LFA-1 lateral mobility, ligand induced generation of a small amount of high affinity LFA-1 and local membrane alignment. I propose that coor dination of these processes allows rapid interconversion between stabl e adhesion and detachment.