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(Received for publication, August 27, 1997, and in revised form, September 25, 1997)
From the 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
Volume 272, Number 49,
Issue of December 5, 1997
pp. 30889-30898
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
Low Affinity Interaction of Human or Rat T Cell Adhesion Molecule
CD2 with Its Ligand Aligns Adhering Membranes to Achieve High
Physiological Affinity
,
,
,
Center for Immunology and Department of
Pathology, Washington University School of Medicine, St. Louis,
Missouri 63110, the ¶ Departments of Biological Chemistry and
Molecular Pharmacology and Medicine, Harvard Medical School,
Hematology-Oncology Division, Brigham and Women's Hospital, Boston,
Massachusetts 02115, 
Biogen Incorporated, Cambridge,
Massachusetts 02142, and the ** Medical Research Council Cellular
Immunology Unit, Sir William Dunn School of Pathology, University of
Oxford, Oxford OX1 3RE, United Kingdom
1) and the interaction
of rat CD2 with its ligand CD48 is of still lower affinity (40 mM1). 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 mM1.
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