CTLA-4 trafficking and surface expression.
The T-cell co-receptor cytotoxic T-cell antigen 4 (CTLA-4) has a strong inhibitory role as shown by the lymphoproliferative phenotype of CTLA-4-deficient mice. Despite its potent effects on T-cell function, CTLA-4 is primarily an intracellular antigen whose surface expression is tightly regulated by restricted trafficking to the cell surface and rapid internalisation. Recently, several signalling molecules such as Trim, PLD, ARF-1 and TIRC7 have been described to be involved in the transport of CTLA-4 to the cell surface. Minor changes in surface expression levels have major effects on the outcome of T-cell activation. Optimal regulation of CTLA-4 surface expression is crucial for the balance of stimulatory and inhibitory signals to maximize protective immune responses while maintaining immunological tolerance and preventing autoimmunity.
Valk
Elke
E
Cell Signalling Section, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
Rudd
Christopher E
CE
Schneider
Helga
H
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D060908:CTLA-4 Antigen; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D021382:Protein Sorting Signals / Q000235:genetics; D021381:Protein Transport / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D021382:Protein Sorting Signals