Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength.
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.
Egen
Jackson G
JG
Howard Hughes Medical Institute, Department of Molecular and Cell Biology, Cancer Research Laboratory, University of California at Berkeley, Berkeley, CA 94720, USA.
Allison
James P
JP
D000069594:Abatacept; D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000737:chemistry; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis / Q000378:metabolism*; D001692:Biological Transport; D018106:CD28 Antigens / Q000032:analysis; D060908:CTLA-4 Antigen; D002450:Cell Communication; D002478:Cells, Cultured; D018796:Immunoconjugates; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013569:Synapses / Q000378:metabolism*; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D000069594:Abatacept