The role of glycosyl phosphatidyl inositol (GPI)-anchored cell surface proteins in T-cell activation.
Glycosylphosphatidylinositol (GPI)-anchored cell surface proteins are widely expressed in tissues, including cells of immunohematopoietic origin. Cross-linking of GPI-linked proteins on T lymphocytes, such as Thy-1 (CD90), Ly-6 A/E, CD48, CD59 and others, induces T-cell mitogenesis. Similar to cross-linking with T-cell receptor (TcR)-specific antibodies, ligation of GPI-anchored proteins induces an intracellular flux of calcium, an up-regulation of activation-associated cell surface proteins and the elaboration of growth-promoting lymphokines. These events are dependent on p56(lck)-mediated tyrosine phosphorylation of substrates. GPI-linked proteins are constitutively clustered in sphingolipid-rich membrane domains. Actin-driven rearrangements of the cytoskeleton are probably responsible for the physical approximation of TcR and GPI-anchored proteins in mature immunological synapses. Functionally, GPI-linked proteins can supplant for signal I and productively collaborate with CD28 to fully activate T cells.
Division of Transplantation, McGill University Health Center, Royal Victoria Hospital, Montreal, QC, Canada. rolf.loertscher@mcgill.ca
Rolf
R
Loertscher
Paula
P
Lavery
D000818:Animals; D018106:CD28 Antigens / Q000502:physiology; D017261:Glycosylphosphatidylinositols / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*
D018106:CD28 Antigens; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell