title: Low affinity interaction of human or rat T cell adhesion molecule CD2 with its ligand aligns adhering membranes to achieve high physiological affinity.
abstract: The mechanism by which low affinity adhesion molecules function to produce stable cell-cell adhesion is unknown. In solution, the interaction of human CD2 with its ligand CD58 is of low affinity (500 mM-1) and the interaction of rat CD2 with its ligand CD48 is of still lower affinity (40 mM-1). At the molecular level, however, the two systems are likely to be topologically identical. Fluorescently labeled glycosylphosphatidylinositol-anchored CD48 and CD58 were prepared and incorporated into supported phospholipid bilayers, in which the ligands were capable of free lateral diffusion. Quantitative fluorescence imaging was used to study the binding of cell surface human and rat CD2 molecules to the fluorescent ligands in contact areas between Jurkat cells and the bilayers. These studies provide two major conclusions. First, CD2/ligand interactions cooperate to align membranes with nanometer precision leading to a physiologically effective two-dimensional affinity. This process does not require the intact cytoplasmic tail of CD2. Second, the degree of membrane alignment that can be achieved by topologically similar receptors deteriorates with decreasing affinity. This suggests an affinity limit for the ability of this mode of cooperativity to achieve stable cell-cell adhesion at approximately 10 mM-1.
authors.affiliation: Center for Immunology and Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Dustin
authors.forename: D E
authors.initials: DE
authors.lastname: Golan
authors.forename: D M
authors.initials: DM
authors.lastname: Zhu
authors.forename: J M
authors.initials: JM
authors.lastname: Miller
authors.forename: W
authors.initials: W
authors.lastname: Meier
authors.forename: E A
authors.initials: EA
authors.lastname: Davies
authors.forename: P A
authors.initials: PA
authors.lastname: van der Merwe
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018801:CD2 Antigens / Q000378:metabolism*; D000071178:CD48 Antigen; D018968:CD58 Antigens / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D008024:Ligands; D008051:Lipid Bilayers / Q000378:metabolism; D008567:Membranes, Artificial; D051381:Rats; D013499:Surface Properties
chemical_list: D015703:Antigens, CD; D018801:CD2 Antigens; D000071178:CD48 Antigen; C000604065:CD48 protein, human; D018968:CD58 Antigens; C000604067:Cd48 protein, rat; D008024:Ligands; D008051:Lipid Bilayers; D008567:Membranes, Artificial; D016650:Fluorescein-5-isothiocyanate