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Multiscale analysis of T cell activation: correlating in vitro and in vivo analysis of the immunological synapse

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Visualizing Immunity

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 334))

Abstract

Recently implemented fluorescence imaging techniques, such as total internal reflection fluorescence microscopy and two-photon laser scanning micro-scopy, have made possible multiscale analysis of the immune response from single molecules in an interface to cells moving in lymphoid tissues and tumors. In this review, we consider components of T cell sensitivity: the immunological synapse, the coordination of migration, and antigen recognition in vivo. Potency, dose, and detection threshold for peptide-MHC determine T cell sensitivity. The immunological synapse incorporates T cell receptor microclusters that initiate and sustain signaling, and it also determines the positional stability of the T cells through symmetry and symmetry breaking. In vivo decisions by T cells on stopping or migration are based of antigen stop signals and environmental go signals that can sometimes prevent arrest of T cells altogether, and thus can change the outcome of antigen encounters.

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Acknowledgements

I acknowledge Mark Philips for valuable discussions on issues of Ras activation in lymphocytes. I thank Rajat Varma, Santosh Vardhana, Julie Huang and Janelle Waite for contributions of ideas and observations that underpin some of the discussion and speculation in this discussion.

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Dustin, M.L. (2009). Multiscale analysis of T cell activation: correlating in vitro and in vivo analysis of the immunological synapse. In: Dustin, M., McGavern, D. (eds) Visualizing Immunity. Current Topics in Microbiology and Immunology, vol 334. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-93864-4_3

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