Mechanisms of Cellular Avidity Regulation in CD2-CD58-Mediated T Cell Adhesion.
The CD2 receptor on T lymphocytes is essential for T cell adhesion and stimulation by antigen presenting cells (APCs). Blockade of CD2 function is immunosuppressive in both model systems and humans, indicating the importance of CD2 for the cellular immune response. Although the affinity of the molecular interaction between CD2 and its counter-receptor, CD58, is relatively low when measured in solution, this interaction mediates tight adhesion within the 2D cell-cell interface. To understand the mechanisms responsible for regulating the avidity of the CD2-CD58 interaction, we measured the number, affinity, and lateral mobility of CD2 molecules on resting and activated T cells. Cell activation caused a 1.5-fold increase in the number of CD2 sites on the cell surface, and the 2D affinity of CD2 for CD58 increased by 2.5-fold. The combination of T cell activation and CD2 ligation to CD58 decreased the laterally mobile fraction of the ligated CD2. Together, these changes would substantially enhance CD2 avidity and strengthen T cell-APC adhesion. The change in CD2 mobile fraction suggests that the cell uses cytoskeletal regulators to immobilize the receptor selectively at the site of contact with surfaces expressing CD58. Our observations are consistent with a model in which T cell activation initially induces increased CD2 2D affinity, cell surface receptor expression, and lateral mobility, allowing the CD2 molecules to diffuse to sites of contact with CD58-bearing APCs. Subsequently, T cell activation causes the CD58-bound CD2 to be recognized and immobilized at sites of cell-cell contact, thereby strengthening T cell-APC adhesion.
Zhu
De-Min
DM
Departments of Biological Chemistry and Molecular Pharmacology, Surgery, and Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
Dustin
Michael L
ML
Cairo
Christopher W
CW
Thatte
Hemant S
HS
Golan
David E
DE
D000915:Antibody Affinity; D000938:Antigen-Presenting Cells / Q000378:metabolism; D018801:CD2 Antigens / Q000096:biosynthesis*; D018968:CD58 Antigens / Q000096:biosynthesis*; D002448:Cell Adhesion; D016650:Fluorescein-5-isothiocyanate / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D019169:Jurkat Cells; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry; D011485:Protein Binding; D020349:Surface Plasmon Resonance; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism
D018801:CD2 Antigens; D018968:CD58 Antigens; D005456:Fluorescent Dyes; D007166:Immunosuppressive Agents; D008051:Lipid Bilayers; D016650:Fluorescein-5-isothiocyanate