医学免疫学课件：Formation of Immunological Synapse

1、Formation of Immunological Synapse1Outline1 The structure of immunological synapse2 Formation of immunological synapse3 Actin-regulatory signaling pathways2Schematic Diagram of the Mature Immunological SynapseRoshni Basu, Morgan Huse null, 2016, Available online 13 December 20163Structure1 cSMACacti

2、vate downstream signaling molecules2 pSMACstable immune synapse structure3 dSMACtransport of LFA-1/ICAM-1 and TCR-MHC4Formation1 Pre-Synapse state: polarization of T cell2 Synapse: microcluster translocation3 Synapse: mature synapse4 Post-synapse: synapse-kinapse transition5polarization of T cell1 C

3、hemotaxis factor2 Lamellipodia formation:actin cytoskeletonChemokine receptoradhesion molecule3 Increase sensitivity of T cells to APC6LFA-1 activation intermediates are organized into a concentric array by a T cellintrinsic mechanism William A. Comrie et al. J Cell Biol 2015;208:475-491William A. C

4、omrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:4

5、75-491William A. et al. Comrie et al. J Cell Biol 2015;208:475-4917Actin polymerization and remodeling at the synapse is critical for TCR microcluster movement to the cSMACSudha Kumari et al. Biochim Biophys Acta. 2014 Feb; 1838(2): 10.10168The model for the segregation of TCR and adhesion molecules

6、 during the immunological synapse formation Yoshihisa Kaizuka et al. PNAS 2007;104:20296-203019Actin polymerization and remodeling at the synapse is critical for TCR microcluster movement to the cSMACSudha Kumari et al. Biochim Biophys Acta. 2014 Feb; 1838(2): 10.101610Cas-L1 A member of a force sen

7、sing protein family2 Amplification of Ca2+ signaling3 Integrin activation4 Actomyosin contraction11Working model illustrating the critical steps that lead to cytoskeletal stretch-dependent Cas-L activation and TCR signalingLus C Santos et al.Immunology and Cell Biology (2016) 94, 981993; doi:10.1038

8、/icb.2016.61 12Mature immune synapse1 Cytoskeleton actin rearrangement2 Stable adhesion complex13L-plastin enables T-cell communication by regulation of LFA-1 cluster formation in the immune synapse William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:47

9、5-491William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491Guido Wabnitz et al. Advances

10、in Biological Regulation, 2016, Available online 27 September 201614TAGLN21 TAGLN2 blocks actin depolymerization2 Competes with cofilin3 Acquiring LFA-1 activation15William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Ce

11、ll Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491Comrie WA et al. Front Immunol. 2016 Mar 7;7:68. doi: 10.3389Reg

12、ulation of the F-actin network at the IS16Regulation of the F-actin network at the IS (part)Comrie WA et al. Front Immunol. 2016 Mar 7;7:68. doi: 10.338917Comrie WA et al. Front Immunol. 2016 Mar 7;7:68. doi: 10.3389Regulation of the F-actin network at the IS (part)18Integrin1 Modulate F-actin flow

13、rates2 VLA-4/VCAM-1 decreases the centripetal flow of F-actin3 Overall effect on the F-actin network depend on Complex signals19Comrie WA et al. Front Immunol. 2016 Mar 7;7:68. doi: 10.3389Regulation of the F-actin network at the IS (part)20William A. Comrie et al. J Cell Biol 2015;208:475-491Willia

14、m A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015

15、;208:475-491Comrie WA et al. Front Immunol. 2016 Mar 7;7:68. doi: 10.3389Regulation of the F-actin network at the IS221 Pre-Synapse state: polarization of T cell2 Synapse: microcluster translocation3 Synapse: mature synapse4 Post-synapse: synapse-kinapse transition21William A. Comrie et al. J Cell B

16、iol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comr

17、ie et al. J Cell Biol 2015;208:475-491Dustin ML. The immunological synapse. Cancer Immunol Res. 2014 Nov;2(11):1023-33.Wabnitz G, Balta E, Samstag Y. L-plastin regulates the stability of the immune synapse of naive and effector T-cells. Adv Biol Regul. 2016 Sep 27. pii: S2212-4926(16)30037-9.Kumari

18、S, Curado S, Mayya V, Dustin ML. T cell antigen receptor activation and actin cytoskeleton remodeling. Biochim Biophys Acta. 2014 Feb;1838(2):546-56.Santos LC, Blair DA, Kumari S, Cammer M, Iskratsch T, Herbin O, Alexandropoulos K, Dustin ML, Sheetz MP. Actin polymerization-dependent activation of C

19、as-L promotes immunological synapse stability. Immunol Cell Biol. 2016 Nov;94(10):981-993.Comrie WA, Babich A, Burkhardt JK. F-actin flow drives affinity maturation and spatial organization of LFA-1 at the immunological synapse. J Cell Biol. 2015 Feb 16;208(4):475-91.Na BR, Kim HR, Piragyte I, Oh HM

20、, Kwon MS, Akber U, Lee HS, Park DS, Song WK, Park ZY, Im SH, Rho MC, Hyun YM, Kim M, Jun CD. TAGLN2 regulates T cell activation by stabilizing the actin cytoskeleton at the immunological synapse. J Cell Biol. 2015 Apr 13;209(1):143-62.22William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491William A. Comrie et al. J Cell Biol 2015;208:475-491Willia