Subcellular dynamics of T cell immunological synapses and kinapses in lymph nodes

In vitro studies have revealed that T cell activation occurs during the formation of either dynamic or stable interactions with antigen-presenting cells (APC), and the respective cell junctions have been referred to as immunological kinapses and synapses. However, the relevance and molecular dynamic...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2010-02, Vol.107 (8), p.3675-3680
Main Authors: Azar, Georges A, Lemaître, Fabrice, Robey, Ellen A, Bousso, Philippe
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - metabolism
Animals
Antigen presentation
B lymphocytes
Biological Sciences
CD4-Positive T-Lymphocytes - immunology
Cell membranes
Cellular biology
Dyes
Fluorescence
Green Fluorescent Proteins - metabolism
Image Processing, Computer-Assisted
Imaging
Immunological synapses
Immunological Synapses - immunology
Immunology
Lymph nodes
Lymph Nodes - immunology
Lymphatic system
Lymphocyte Activation
Lymphocytes
Membrane Proteins - metabolism
Mice
Mice, Inbred BALB C
Phosphoproteins - metabolism
Synapses
T cell antigen receptors
T lymphocytes
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Summary:In vitro studies have revealed that T cell activation occurs during the formation of either dynamic or stable interactions with antigen-presenting cells (APC), and the respective cell junctions have been referred to as immunological kinapses and synapses. However, the relevance and molecular dynamics of kinapses and synapses remain to be established in vivo. Using two-photon imaging, we tracked the distribution of LAT-EGFP molecules during antigen recognition by activated CD4⁺ T cells in lymph nodes. At steady state, LAT-EGFP molecules were preferentially found at the uropod of rapidly migrating T cells. In contrast to naïve T cells that fully stopped upon systemic antigen delivery, recently activated T cells decelerated and formed kinapses, characterized by continuous extension of membrane protrusions and by the absence of persistent LAT-EGFP clustering. On the other hand, activated CD4⁺ T cells formed stable immunological synapses with antigen-loaded B cells and displayed sustained accumulation of LAT-EGFP fluorescence at the contact zone. Our results show that the state of T cell activation and the type of APC largely influence T cell-APC contact dynamics in lymph nodes. Furthermore, we provide a dynamic look at immunological kinapses and synapses in lymph nodes and suggest the existence of distinct patterns of LAT redistribution during antigen recognition.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0905901107