Cutting edge: TCR engagement and triggering in the absence of large-scale molecular segregation at the T cell-APC contact site.
We investigated the functional role of large-scale molecular segregation at the T cell-APC contact site during T lymphocyte Ag recognition. Inhibition of CD2-CD58 interaction markedly affected segregation of CD2 and CD2AP from CD45. Under these conditions, Ag-induced calcium mobilization, PKC theta; clustering at the immunological synapse, and IFN-gamma production also were inhibited. However, early TCR signaling and T cell polarization toward APCs were unaffected. Our results indicate that the "raison d'être" of a large-scale segregation of surface molecules and intracellular enzymes and adapters, in Ag-stimulated T cells, is to reinforce the assembly of the signal transduction cascade rather than favor TCR engagement and triggering.
Zaru
Rossana
R
Institut National de la Santé et de la Recherche Médicale Unité 536, Institut Claude de Préval, Toulouse, France.
Cameron
Thomas O
TO
Stern
Lawrence J
LJ
Müller
Sabina
S
Valitutti
Salvatore
S
D048868:Adaptor Proteins, Signal Transducing; D000938:Antigen-Presenting Cells / Q000276:immunology*; D018801:CD2 Antigens / Q000502:physiology; D018968:CD58 Antigens / Q000378:metabolism; D002461:Cell Line, Transformed; D016764:Cell Polarity; D002999:Clone Cells; D003598:Cytoskeletal Proteins; D007371:Interferon-gamma / Q000096:biosynthesis; D046911:Macromolecular Substances; D011506:Proteins / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000648:ultrastructure
D048868:Adaptor Proteins, Signal Transducing; D018801:CD2 Antigens; C114545:CD2-associated protein; D018968:CD58 Antigens; D003598:Cytoskeletal Proteins; D046911:Macromolecular Substances; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma