Part I: Antigen Recognition
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In his first lecture, Dustin explains that adaptive immunity allows an individual to specifically recognize and respond to a vast number of molecules. B cells recognize intact antigens and produce neutralizing antibodies. T cells, on the other hand, have receptors on their surface that recognize very small antigen fragments bound to MHC on the surface of antigen presenting cells (APC). Dustin explains that T cells overcome the challenges of finding and binding to the APCs with the help of a multitude of adhesion molecules. Once the T cell receptor has bound a peptide antigen, an immunological synapse, with its typical bulls-eye structure, is formed resulting in T cell activation.
In Part 2, Dustin describes how a reconstituted system has allowed the immunological synapse to be studied in molecular detail. It is possible to visualize the localization of signaling molecules such as kinases, and determine the role of the actin cytoskeleton in regulating this localization. Dustin also touches on the role of the immunological synapse in autoimmune disease and cancer.
In his last lecture, Dustin presents work from his lab showing that T cell receptor enriched vesicles are generated in the immunological synapse. These vesicles can be transferred to B cells leading to activation of the B cells and, potentially, the production of higher specificity antibodies.
Michael Dustin is Professor of Immunology and Director of Research at The Kennedy Institute of Rheumatology at the University of Oxford. Prior to joining the Kennedy Institute, Dustin was a faculty member at the Skirball Institute of Biomolecular Medicine at New York University from 2001-2013 and at Washington University School of Medicine from 1993-2000. Dustin received his BA in Biology from Boston University and his PhD in Cell and Developmental Biology from Harvard University.
As described in his iBioSeminar, Dustin’s lab studies the molecular events that take place at the immunological synapse. Future research will focus on developing therapies targeted to the immunological synapse to cure chronic inflammatory illnesses such as rheumatoid arthritis.
Dustin is an active participant in the immunology community; he is a member of numerous grant review committees and journal editorial boards. His research has been recognized with many awards including the 2000 Presidential Early Career Award in Science and Engineering and the 2012 DART-NYU Biotechnology Achievement Award.
- Avery August iBioSeminar: Allergies and the Immune System
- Diane Mathis iBioSeminar: T Cell Tolerance
- Ira Mellman iBioSeminar: Cell Biology of the Immune Response
- Ira Mellman iBioEducation: The Immune System
Dustin ML. (2014) The immunological synapse. Cancer immunology research. 2(11):1023-33. Review.
Monks CR, Freiberg BA, Kupfer H, Sciaky N, Kupfer A. (1998) Three-dimensional segregation of supramolecular activation clusters in T cells. Nature. 395(6697):82-6.
Grakoui A, Bromley SK, Sumen C, Davis MM, Shaw AS, Allen PM, Dustin ML. (1999) The immunological synapse: a molecular machine controlling T cell activation. Science. 285(5425):221-7.
Yokosuka T, Sakata-Sogawa K, Kobayashi W, Hiroshima M, Hashimoto-Tane A, Tokunaga M, Dustin ML, Saito T. (2005) Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of Zap70 and SLP-76. Nat Immunol. 6:1253-62.
Kaizuka Y, Douglass AD, Varma R, Dustin ML, Vale RD. (2007) Mechanisms for segregating T cell receptor and adhesion molecules during immunological synapse formation in Jurkat T cells. Proc Natl Acad Sci U S A. 104(51):20296-301.
Choudhuri K, Llodra J, Roth EW, Tsai J, Gordo S, Wucherpfennig KW, Kam LC, Stokes DL, Dustin ML. (2014) Polarized release of T-cell-receptor-enriched microvesicles at the immunological synapse. Nature. 507(7490):118-23.
Ritter AT, Asano Y, Stinchcombe JC, Dieckmann NM, Chen BC, Gawden-Bone C, van Engelenburg S, Legant W, Gao L, Davidson MW, Betzig E, Lippincott-Schwartz J, Griffiths GM. (2015) Actin depletion initiates events leading to granule secretion at the immunological synapse. Immunity. 42(5):864-76.