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.
MeSH terms
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Abatacept
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Animals
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Antigens, CD / physiology
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Antigens, Differentiation / physiology
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CD3 Complex / physiology
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CTLA-4 Antigen
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Cell Survival
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Fas Ligand Protein
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Glycosylphosphatidylinositols / deficiency
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Glycosylphosphatidylinositols / genetics
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Glycosylphosphatidylinositols / physiology*
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Hemoglobinuria, Paroxysmal / genetics
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Homeostasis / physiology*
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Humans
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Immunoconjugates*
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Interleukin-2 / physiology
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Lymphocyte Activation / physiology*
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Membrane Glycoproteins / physiology
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Membrane Lipids / physiology
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Membrane Proteins / deficiency
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Membrane Proteins / genetics
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Membrane Proteins / physiology
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Mice
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Mice, Knockout
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Phenotype
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Phosphatidylinositols / physiology
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Protein Structure, Tertiary
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Receptors, Antigen, T-Cell / immunology
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Signal Transduction
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T-Lymphocyte Subsets / cytology*
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T-Lymphocyte Subsets / immunology
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X Chromosome / genetics
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fas Receptor / physiology
Substances
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Antigens, CD
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Antigens, Differentiation
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CD3 Complex
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CD3 antigen, zeta chain
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CTLA-4 Antigen
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CTLA4 protein, human
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Ctla4 protein, mouse
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FASLG protein, human
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Fas Ligand Protein
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Fasl protein, mouse
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Glycosylphosphatidylinositols
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Immunoconjugates
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Interleukin-2
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Membrane Glycoproteins
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Membrane Lipids
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Membrane Proteins
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Phosphatidylinositols
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Receptors, Antigen, T-Cell
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fas Receptor
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phosphatidylinositol glycan-class A protein
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Abatacept