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Selective Inhibition of T Cell Activation Via CD147 Through Novel Modulation of Lipid Rafts¹

Günther Staffler^2,*, Andreas Szekeres^*, Gerhard J. Schütz, Marcus D. Säemann^*, Elisabeth Prager^*, Maximilian Zeyda, Karel Drbal, Gerhard J. Zlabinger^*, Thomas M. Stulnig and Hannes Stockinger^3,*,

^* Institute of Immunology, University of Vienna, Vienna, Austria; Institute for Biophysics, University of Linz, Linz, Austria; and Department of Internal Medicine III, University of Vienna, Vienna, Austria; and Competence Center for Biomolecular Therapeutics, Vienna, Austria

The plasma membrane is compartmentalized into microdomains and the association/dissociation of receptors and signaling molecules with/from these membrane domains is a major principle for regulation of signal transduction. By following the reorganization of microdomains on living cells and performing biochemical studies, we show that Ab targeting of the T cell activation-associated Ag CD147 prevents TCR stimulation-dependent reorganization and clustering of microdomains. Triggering CD147 induces a displacement of the GPI-anchored coreceptors CD48 and CD59 from microdomains in human T lymphocytes. This perturbation of microdomains is accompanied by a selective inhibition of TCR-mediated T cell proliferation. The CD147-inhibited cells secret normal levels of IL-2 but acquire reduced amounts of the IL-2 receptor -chain CD25. These results indicate that negative regulating signals can modulate microdomains and suggest a general mechanism for inhibition of receptor signaling.

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