Co-stimulation and counter-stimulation: lipid raft clustering controls TCR signaling and functional outcomes.
T cell receptor (TCR) antigen recognition induces the formation of a specialized 'immunological synapse' at the T cell : antigen presenting cell (APC) junction. This junction is generated by the recruitment and exclusion of particular proteins from the contact area and is required for T cell activation. We and others have hypothesized that lipid raft/non-raft partitioning provides a molecular basis for protein sorting which organizes the TCR, co-stimulators, signal transducers and the actin cytoskeleton at the T cell : APC interface. Here we discuss the emerging paradigm that co-stimulators induce the directional transport and clustering of lipid rafts at the T cell : APC interface, thus generating platform(s) specialized for processive and sustained TCR signal transduction and T cell activation. We also discuss recent data implicating the involvement of 'counter-stimulators' and other negative regulators which prevent optimal raft clustering at the TCR contact site and, thus, facilitate T cell inactivation and tolerance induction.
Miceli
M C
MC
Department of Microbiology, Immunology and Molecular Genetics, UCLA School of Medicine, Los Angeles, CA 90095-1570, USA. cmiceli@ucla.edu
Moran
M
M
Chung
C D
CD
Patel
V P
VP
Low
T
T
Zinnanti
W
W
D000818:Animals; D001665:Binding Sites; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D003599:Cytoskeleton / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D021962:Membrane Microdomains / Q000276:immunology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D017634:Self Tolerance / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014443:Tyrosine / Q000378:metabolism
D011948:Receptors, Antigen, T-Cell; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases