The function of GPI-anchored proteins in T cell development, activation and regulation of homeostasis

J Biol Regul Homeost Agents. Apr-Jun 2000;14(2):99-115.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Abatacept
  • Animals
  • Antigens, CD / physiology
  • Antigens, Differentiation / physiology
  • CD3 Complex / physiology
  • CTLA-4 Antigen
  • Cell Survival
  • Fas Ligand Protein
  • Glycosylphosphatidylinositols / deficiency
  • Glycosylphosphatidylinositols / genetics
  • Glycosylphosphatidylinositols / physiology*
  • Hemoglobinuria, Paroxysmal / genetics
  • Homeostasis / physiology*
  • Humans
  • Immunoconjugates*
  • Interleukin-2 / physiology
  • Lymphocyte Activation / physiology*
  • Membrane Glycoproteins / physiology
  • Membrane Lipids / physiology
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology
  • Mice
  • Mice, Knockout
  • Phenotype
  • Phosphatidylinositols / physiology
  • Protein Structure, Tertiary
  • Receptors, Antigen, T-Cell / immunology
  • Signal Transduction
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology
  • X Chromosome / genetics
  • fas Receptor / physiology

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • CD3 Complex
  • CD3 antigen, zeta chain
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Ctla4 protein, mouse
  • FASLG protein, human
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Glycosylphosphatidylinositols
  • Immunoconjugates
  • Interleukin-2
  • Membrane Glycoproteins
  • Membrane Lipids
  • Membrane Proteins
  • Phosphatidylinositols
  • Receptors, Antigen, T-Cell
  • fas Receptor
  • phosphatidylinositol glycan-class A protein
  • Abatacept