Immunological synapse
In immunology, an immunological synapse (or immune synapse) is the interface between an antigen-presenting cell or target cell and a lymphocyte such as an effector T cell or Natural Killer cell.[1] It is the subject of much ongoing research.[2]
Structure and Function
The immune synapse is also known as the supramolecular activation cluster or SMAC.[3] This structure is composed of concentric rings each containing segregated clusters of proteins:
- c-SMAC (central-SMAC) composed of the θ isoform of protein kinase C,[4] CD2, CD4, CD8, CD28, Lck, and Fyn.[5]
- p-SMAC (peripheral-SMAC) within which the lymphocyte function-associated antigen-1 (LFA-1) and the cytoskeletal protein talin are clustered.[3]
- d-SMAC (distal-SMAC) enriched in CD43 and CD45 molecules.[6][7]
This complex as a whole is postulated to have several functions including but not limited to:
- Regulation of lymphocyte activation[8]
- Transfer of peptide-MHC complexes from APCs to lymphocytes[8]
- Direct secretion of cytokines or lytic granules[8]
History
It was first discovered by Abraham Kupfer at the National Jewish Medical and Research Center in Denver and the term was coined by Michael Dustin at NYU who studied it in further detail. Daniel Davis and Jack Strominger showed structured immune synapses for a different lymphocyte, the Natural Killer cell, and published this around the same time.[9] Abraham Kupfer first presented his findings during one of the Keystone symposia in 1995, when he showed three-dimensional images of immune cells interacting with one another. Key molecules in the synapse are the T cell receptor and its counterpart the major histocompatibility complex (MHC). Also important are LFA-1, ICAM-1, CD28, and CD80/CD86.
References
- ↑ Grakoui A, Bromley SK, Sumen C, Davis MM, Shaw AS, Allen PM, Dustin ML (July 1999). "The immunological synapse: a molecular machine controlling T cell activation". Science 285 (5425): 221–227. doi:10.1126/science.285.5425.221. PMID 10398592.
- ↑ "What is the importance of the immunological synapse?" (PDF).
- 1 2 Monks CR, Freiberg BA, Kupfer H, Sciaky N, Kupfer A (September 1998). "Three-dimensional segregation of supramolecular activation clusters in T cells". Nature 395 (6697): 82–86. doi:10.1038/25764. PMID 9738502.
- ↑ Monks CR, Kupfer H, Tamir I, Barlow A, Kupfer A (January 1997). "Selective modulation of protein kinase C-theta during T-cell activation". Nature 385 (6611): 83–86. doi:10.1038/385083a0. PMID 8985252.
- ↑ Lee KH, Holdorf AD, Dustin ML, Chan AC, Allen PM, Shaw AS (February 2002). "T cell receptor signaling precedes immunological synapse formation". Science 295 (5559): 1539–1542. doi:10.1126/science.1067710. PMID 11859198.
- ↑ Delon J, Kaibuchi K, Germain RN (November 2001). "Exclusion of CD43 from the immunological synapse is mediated by phosphorylation-regulated relocation of the cytoskeletal adaptor moesin". Immunity 15 (5): 691–701. doi:10.1016/S1074-7613(01)00231-X. PMID 11728332.
- ↑ Freiberg BA, Kupfer H, Maslanik W, Delli J, Kappler J, Zaller DM, Kupfer A (October 2002). "Staging and resetting T cell activation in SMACs". Nat. Immunol. 3 (10): 911–917. doi:10.1038/ni836. PMID 12244310.
- 1 2 3 Davis, DM; Dustin, ML (June 2004). "What is the importance of the immunological synapse?". Trends in immunology 25 (6): 323–7. doi:10.1016/j.it.2004.03.007. PMID 15145322.
- ↑ Davis DM, Chiu I, Fassett M, Cohen GB, Mandelboim O, Strominger JL (Dec 1999). "The human natural killer cell immune synapse". Proc Natl Acad Sci U S A 96 (26): 15062–7. doi:10.1073/pnas.96.26.15062. PMC 24773. PMID 10611338.