The function of GPI-anchored proteins in T cell development, activation and regulation of homeostasis.
Many glycosylphosphatidyl-inositol-anchored proteins (GPI-AP) are expressed on T lymphocytes. Ligand or mAb-mediated aggregation of all GPI-AP tested to date results in the initiation of signal transduction pathways via the activation of src family protein tyrosine kinases. Src family kinases co-localise with GPI-AP in specialised sub-domains of the plasma membrane, referred to as detergent insoluble membrane microdomains (DIGS), which are thought to function as signalling platforms. GPI-AP may play a role in the regulation of T cell clonal expansion and effector functions at multiple levels, including the initiation of T cell activation through the antigen receptor complex, the regulation of ongoing responses supported by persisting antigen, as well as proliferative responses to the major T cell growth factor, IL-2. Evidence supporting the role of GPI-AP in the regulation of T cell development, activation and homeostasis is discussed, as well as insights provided by studies in humans and mice lacking GPI-AP.
Marmor
M D
MD
Department of Immunology, University of Toronto, Ontario, Canada.
Julius
M
M
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D000943:Antigens, Differentiation / Q000502:physiology; D017252:CD3 Complex / Q000502:physiology; D060908:CTLA-4 Antigen; D002470:Cell Survival; D053222:Fas Ligand Protein; D017261:Glycosylphosphatidylinositols / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D018796:Immunoconjugates; D007376:Interleukin-2 / Q000502:physiology; D008213:Lymphocyte Activation / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000502:physiology; D008563:Membrane Lipids / Q000502:physiology; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D010716:Phosphatidylinositols / Q000502:physiology; D017434:Protein Structure, Tertiary; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D014960:X Chromosome / Q000235:genetics; D019014:fas Receptor / Q000502:physiology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D017261:Glycosylphosphatidylinositols; D018796:Immunoconjugates; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D008563:Membrane Lipids; D008565:Membrane Proteins; D010716:Phosphatidylinositols; D011948:Receptors, Antigen, T-Cell; D019014:fas Receptor; C080086:phosphatidylinositol glycan-class A protein; D000069594:Abatacept