Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength

Immunity. 2002 Jan;16(1):23-35. doi: 10.1016/s1074-7613(01)00259-x.


CD28 and CTLA-4 engagement with B7 expressed by APCs generates critical regulatory signals for T cell activation. CD28 is expressed on the T cell surface and enhances T cell expansion, while CTLA-4 localizes primarily to an intracellular compartment and inhibits T cell proliferation. We demonstrate that CTLA-4 has several unique trafficking properties that may regulate its ability to attenuate a T cell response. Importantly, accumulation of CTLA-4 at the immunological synapse is proportional to the strength of the TCR signal, suggesting that cells receiving stronger stimuli are more susceptible to CTLA-4-mediated inhibition. This may represent a novel feedback control mechanism in which a stimulatory signal regulates the recruitment of an inhibitory receptor to a functionally relevant site on the cell surface.

Publication types

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

MeSH terms

  • Abatacept
  • Amino Acid Sequence
  • Animals
  • Antigen-Presenting Cells / chemistry
  • Antigens, CD
  • Antigens, Differentiation / analysis
  • Antigens, Differentiation / metabolism*
  • Biological Transport
  • CD28 Antigens / analysis
  • CTLA-4 Antigen
  • Cell Communication
  • Cells, Cultured
  • Immunoconjugates*
  • Interleukin-2 / biosynthesis
  • Lymphocyte Activation
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Receptors, Antigen, T-Cell / physiology*
  • Synapses / metabolism*
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / immunology*


  • Antigens, CD
  • Antigens, Differentiation
  • CD28 Antigens
  • CTLA-4 Antigen
  • Ctla4 protein, mouse
  • Immunoconjugates
  • Interleukin-2
  • Receptors, Antigen, T-Cell
  • Abatacept