The Journal of Immunology, Vol 144, Issue 3 860-868, Copyright © 1990 by American Association of Immunologists

ARTICLES

Role of phosphatidylinositol-anchored proteins in T cell activation

DH Presky, MG Low and EM Shevach
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.

A novel class of cell surface proteins are attached to the plasma membrane via a phosphatidylinositol (PI)-glycan anchoring structure, and these proteins can be selectively removed from the cell surface by the enzyme PI-specific phospholipase C (PI-PLC). Enzyme treatment led to a prolonged reduction in cell surface expression of several PI- anchored proteins. Activation of T cells led to a marked decrease in the ability of PI-PLC to remove PI-anchored surface proteins from the activated T cells. This decrease in PI-PLC sensitivity may reflect an alteration in the PI-glycan anchoring structures, or in a general membrane property, which renders the PI-anchored proteins inaccessible to the enzyme. When murine T lymphocytes were treated with PI-PLC and then stimulated with either Con A, the calcium ionophore A23187 and PMA, or an anti-CD3 mAb, the response to Con A stimulation was inhibited by 90%, whereas the responses to ionophore and PMA or anti- CD3 were not affected. Removal of PI-anchored proteins inhibited an early event in the activation process in response to Con A because both IL-2 production and IL-2R expression were inhibited by the PI-PLC treatment. Inhibition of the Con A response was secondary to removal of a PI-linked protein from the responder T cell population because PI-PLC treatment of T-depleted spleen cells did not alter their ability to act as a source of accessory cells. It is unlikely that removal of the known PI-linked proteins on murine T cells, Thy-1 and Ly-6, can fully account for the inhibition of Con A response because the cell line M2B3, that lacks these surface proteins, responded normally to Con A stimulation. These studies demonstrate that one or more PI-anchored T cell proteins play an important role in an early step of Con A activation, perhaps involving T cell-accessory cell interactions. In contrast, the ability to stimulate T cells by direct cross-linking of TCR/CD3 complex is not dependent on the presence of these PI-anchored proteins.

This article has been cited by other articles:

				R. Linden, V. R. Martins, M. A. M. Prado, M. Cammarota, I. Izquierdo, and R. R. Brentani Physiology of the Prion Protein Physiol Rev, April 1, 2008; 88(2): 673 - 728. [Abstract] [Full Text] [PDF]

				G. Terrazzano, M. Sica, C. Becchimanzi, S. Costantini, B. Rotoli, S. Zappacosta, F. Alfinito, and G. Ruggiero T cells from paroxysmal nocturnal haemoglobinuria (PNH) patients show an altered CD40-dependent pathway J. Leukoc. Biol., July 1, 2005; 78(1): 27 - 36. [Abstract] [Full Text] [PDF]

				A. Khalili-Shirazi, S. Quaratino, M. Londei, L. Summers, M. Tayebi, A. R. Clarke, S. H. Hawke, G. S. Jackson, and J. Collinge Protein Conformation Significantly Influences Immune Responses to Prion Protein J. Immunol., March 15, 2005; 174(6): 3256 - 3263. [Abstract] [Full Text] [PDF]

				S. M. M. Haeryfar and D. W. Hoskin Thy-1: More than a Mouse Pan-T Cell Marker J. Immunol., September 15, 2004; 173(6): 3581 - 3588. [Abstract] [Full Text] [PDF]

				G. Staffler, A. Szekeres, G. J. Schutz, M. D. Saemann, E. Prager, M. Zeyda, K. Drbal, G. J. Zlabinger, T. M. Stulnig, and H. Stockinger Selective Inhibition of T Cell Activation Via CD147 Through Novel Modulation of Lipid Rafts J. Immunol., August 15, 2003; 171(4): 1707 - 1714. [Abstract] [Full Text] [PDF]

				D. M. Cerasoli, G. Kelsoe, and M. Sarzotti CD4+Thy1- thymocytes with a Th-type 2 cytokine response Int. Immunol., January 1, 2001; 13(1): 75 - 83. [Abstract] [Full Text] [PDF]

				F. Y. S. Chuang, M. Sassaroli, and J. C. Unkeless Convergence of Fc{gamma} Receptor IIA and Fc{gamma} Receptor IIIB Signaling Pathways in Human Neutrophils J. Immunol., January 1, 2000; 164(1): 350 - 360. [Abstract] [Full Text] [PDF]

				S. J. Richards, G. J. Morgan, and P. Hillmen Analysis of T Cells in Paroxysmal Nocturnal Hemoglobinuria Provides Direct Evidence That Thymic T-Cell Production Declines With Age Blood, October 15, 1999; 94(8): 2790 - 2799. [Abstract] [Full Text] [PDF]