Intracellular trafficking of CTLA-4 and focal localization towards sites of TCR engagement

Immunity. 1996 Jun;4(6):535-43. doi: 10.1016/s1074-7613(00)80480-x.


T lymphocyte receptor CTLA-4 binds costimulatory molecules CD80 (B7-1) and CD86 (B7-2) with high avidity and negatively regulates T cell activation. CTLA-4 functions at the cell surface, yet is primarily localized in intracellular vesicles. Here, we demonstrate cycling of CTLA-4 between intracellular stores and the cell surface. Intracellular vesicles containing CTLA-4 overlapped with endocytic compartment(s) and with perforin-containing secretory granules. Cell surface expression of CTLA-4 was rapidly increased by raising intracellular calcium levels. During T cell activation, intracellular and cell surface CTLA-4 became focused towards sites of TCR activation. Cycling and directional control of CTLA-4 expression may regulate its functional interaction with APCs bearing peptide-MHC complexes of appropriate specificity and avidity.

MeSH terms

  • Abatacept
  • Antigens, CD / metabolism*
  • Antigens, Differentiation / metabolism*
  • B7-1 Antigen / metabolism*
  • B7-2 Antigen
  • Biological Transport / immunology
  • CTLA-4 Antigen
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Cell Polarity / immunology
  • Cells, Cultured
  • Endosomes / immunology
  • Endosomes / metabolism
  • Humans
  • Immunoconjugates*
  • Intracellular Fluid / immunology
  • Intracellular Fluid / metabolism
  • Membrane Glycoproteins / metabolism*
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • Receptors, Antigen, T-Cell / metabolism*
  • Up-Regulation / immunology


  • Antigens, CD
  • Antigens, Differentiation
  • B7-1 Antigen
  • B7-2 Antigen
  • CD86 protein, human
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Immunoconjugates
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Receptors, Antigen, T-Cell
  • Perforin
  • Abatacept