Increased TCR avidity after T cell activation: a mechanism for sensing low-density antigen.
While activated T cells are known to have enhanced biological responses to antigen stimulation, the biophysical basis of this increased sensitivity remains unknown. Here, we show that, on activated T cells, the TCR avidity for peptide-MHC complexes is 20- to 50-fold higher than the TCR avidity of naive T cells. This increased avidity for peptide-MHC depends on TCR reorganization and is sensitive to the cholesterol content of the T cell membrane. Analysis of the binding data indicates the enhanced avidity is due to increases in cross-linking of TCR on activated T cells. Activation-induced membrane (AIM) changes in TCR avidity represent a previously unrecognized means of increasing the sensitivity of activated T cells to small amounts of antigen in the periphery.
Department of Pathology and Medicine, Division of Immunopathology, Johns Hopkins University, Baltimore, MD 21218, USA. tarekf2000@yahoo.com
T M
TM
Fahmy
J G
JG
Bieler
M
M
Edidin
J P
JP
Schneck
D000818:Animals; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D003432:Cross-Linking Reagents; D019281:Dimerization; D006183:H-2 Antigens / Q000737:chemistry / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008213:Lymphocyte Activation; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D010455:Peptides / Q000378:metabolism; D020836:Protein Structure, Quaternary; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D003432:Cross-Linking Reagents; D006183:H-2 Antigens; D008563:Membrane Lipids; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D002784:Cholesterol