A large T cell invagination with CD2 enrichment resets receptor engagement in the immunological synapse.
T cell activation is driven by the TCR and complemented by costimulation. We have studied the dynamics of ligand-engagement of the costimulatory receptor CD2 in T cell/APC couples. Thousands of ligand-engaged CD2 molecules were included in a large T cell invagination at the center of the cellular interface within 1 min of cell couple formation. The structure and regulation of this invagination shared numerous features with phagocytosis and macropinocytosis. Three observations further characterize the invagination and the inclusion of CD2: 1) numerous ligand-engaged receptors were enriched in and internalized through the T cell invagination, none as prominently as CD2; 2) dissolution of the T cell invagination and CD2 engagement were required for effective proximal T cell signaling; and 3) the T cell invagination was uniquely sensitive to the affinity of the TCR for peptide-MHC. Based on this characterization, we speculate that the T cell invagination, aided by CD2 enrichment, internalizes parts of the TCR signaling machinery to reset T cell signaling upon agonist-mediated, stable APC contact.
Singleton
Kentner
K
Center for Immunology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Parvaze
Nadia
N
Dama
Kavyya R
KR
Chen
Kenneth S
KS
Jennings
Paula
P
Purtic
Bozidar
B
Sjaastad
Michael D
MD
Gilpin
Christopher
C
Davis
Mark M
MM
Wülfing
Christoph
C
D000199:Actins / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000648:ultrastructure*; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D018801:CD2 Antigens / Q000276:immunology / Q000378:metabolism*; D000071178:CD48 Antigen; D004705:Endocytosis / Q000276:immunology; D007091:Image Processing, Computer-Assisted; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure*
D000199:Actins; D015703:Antigens, CD; D018801:CD2 Antigens; D000071178:CD48 Antigen; D011948:Receptors, Antigen, T-Cell