Cofilin peptide homologs interfere with immunological synapse formation and T cell activation.
The formation of supramolecular activation clusters within the immunological synapse, crucial for sustained signaling and T lymphocyte activation, requires costimulation-dependent reorganization of the actin cytoskeleton. Here we have identified the actin-remodeling protein cofilin as a key player in this process. Cell-permeable peptides that block costimulation-induced cofilin/F-actin interactions in untransformed human T lymphocytes impair receptor capping and immunological synapse formation at the interface between T cells and antigen-presenting cells. As a consequence, T cell activation, as measured by cytokine production and proliferation, is inhibited.
Eibert
Sybille M
SM
Institute for Immunology, Ruprecht-Karls-University, D-69120 Heidelberg, Germany.
Lee
Kyeong-Hee
KH
Pipkorn
Rüdiger
R
Sester
Urban
U
Wabnitz
Guido H
GH
Giese
Thomas
T
Meuer
Stefan C
SC
Samstag
Yvonne
Y
D051339:Actin Depolymerizing Factors; D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D018801:CD2 Antigens / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D057846:Cell-Penetrating Peptides; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007152:Immunologic Capping / Q000187:drug effects; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008840:Microfilament Proteins / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
D051339:Actin Depolymerizing Factors; D000199:Actins; D018801:CD2 Antigens; D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D016207:Cytokines; D007519:Isoantigens; D008840:Microfilament Proteins; D010455:Peptides; C414409:penetratin