Signaling Amplification at the Immunological Synapse
The immunological synapse is a dynamic structure, formed between a T cell and one or more antigen-presenting cells, characterized by lipid and protein segregation, signaling compartmentalization, and bidirectional information exchange through soluble and membrane-bound transmitters. In addition, the immunological synapse is the site where signals delivered by the T-cell receptors, adhesion molecules, as well as costimulatory and coinhibitory receptors are decoded and integrated. Signaling modulation and tunable activation thresholds allow T cells to interpret the context in which the antigen is presented, recognize infectious stimuli, and finally decide between activation and tolerance. In this review, we discuss some strategies used by membrane receptors to tune activation signals in T cells.
KeywordsChemokine Receptor Immunological Synapse Membrane Raft CD28 Costimulation Immune Synapse
A.V. is supported by the Italian Association for Cancer Research (AIRC); Telethon; Ministero dell’Università e della Ricerca (MIUR); Istituto Superiore di Sanità; Alleanza Contro il Cancro; the DoD Army Medical Research, USA; the Cancer Research Institute of New York; the EMBO Young Investigator Program; E-rare 2007; EC FP7 HEALTH-F4-2008-201106.
- Calvo CR, Amsen D, Kruisbeek AM (1997) Cytotoxic T lymphocyte antigen 4 (CTLA-4) interferes with extracellular signal-regulated kinase (ERK) and Jun NH2-terminal kinase (JNK) activation, but does not affect phosphorylation of T cell receptor zeta and ZAP70. J Exp Med 186:1645–1653CrossRefPubMedGoogle Scholar
- Paccani SR, Boncristiano M, Patrussi L, Ulivieri C, Wack A, Valensin S, Hirst TR, Amedei A, Del Prete G, Telford JL, D'Elios MM, Baldari CT (2005) Defective Vav expression and impaired F-actin reorganization in a subset of patients with common variable immunodeficiency characterized by T-cell defects. Blood 106:626–634CrossRefPubMedGoogle Scholar
- Raab M, Cai YC, Bunnell SC, Heyeck SD, Berg LJ, Rudd CE (1995) p56Lck and p59Fyn regulate CD28 binding to phosphatidylinositol 3-kinase, growth factor receptor-bound protein GRB-2, and T cell-specific protein-tyrosine kinase ITK: implications for T-cell costimulation. Proc Natl Acad Sci USA 92:8891–8895CrossRefPubMedGoogle Scholar
- Shamri R, Grabovsky V, Gauguet JM, Feigelson S, Manevich E, Kolanus W, Robinson MK, Staunton DE, von Andrian UH, Alon R (2005) Lymphocyte arrest requires instantaneous induction of an extended LFA-1 conformation mediated by endothelium-bound chemokines. Nat Immunol 6:497–506CrossRefPubMedGoogle Scholar