CTLA-4 trafficking and surface expression

Trends Immunol. 2008 Jun;29(6):272-9. doi: 10.1016/j.it.2008.02.011. Epub 2008 May 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antigens, CD / chemistry
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Antigens, CD / metabolism*
  • CTLA-4 Antigen
  • Gene Expression Regulation / immunology*
  • Humans
  • Immune Tolerance
  • Lymphocyte Activation
  • Protein Sorting Signals / genetics
  • Protein Transport / immunology
  • Signal Transduction / immunology


  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Ctla4 protein, mouse
  • Protein Sorting Signals