Abstract
Polarization of T cells towards the antigen presenting cell (APC) is critically important for appropriate activation and differentiation of the naïve T cell. Here we used imaging flow cytometry (IFC) and show that the activation induced Lck and Itk adapter T cell specific adapter protein (TSAd), encoded by SH2D2A, modulates polarization of T cells towards the APC. Upon exposure to APC presenting the cognate antigen Id, Sh2d2a−/− CD4+ T cells expressing Id-specific transgenic T cell receptor (TCR), displayed impaired polarization of F-actin and TCR to the immunological synapse (IS). Sh2d2a−/− T-cells that did polarize F-actin and TCR still displayed impaired polarization of PKCξ, PAR3 and the microtubule-organizing center (MTOC). In vitro differentiation of activated Sh2d2a−/− T cells was skewed towards an effector memory (Tem) rather than a central memory (Tcm) phenotype. A similar trend was observed for Id-specific TCR Sh2d2a−/− T cells stimulated with APC and cognate antigen. Taken together our data suggest that TSAd modulates differentiation of experienced T cells possibly through polarization of CD4+ T cells towards the APC.
Highlights
Upon stimulation of T cells via T cell receptor (TCR) and other surface receptors, initiation of signalling cascades eventually results in proliferation and differentiation into various T cell phenotypes[1]
T cell specific adapter protein (TSAd) expression is induced in T cells upon activation through the TCR/CD3 complex[15,16]
The amount of TSAd in CD3/CD28 activated human CD4+ T cells was measured in dividing cells using cell tracker violet (CTV) dilution combined with intracellular staining for TSAd
Summary
Upon stimulation of T cells via TCR and other surface receptors, initiation of signalling cascades eventually results in proliferation and differentiation into various T cell phenotypes[1]. The molecular details for how signalling in T cells is controlled after the initial triggering of the TCR is not fully understood. Polarisation of actin, TCR and signalling molecules towards the IS are required for proper activation and function of T cells, where CD4+ T cells engage with the APC for several hours[1]. Upon triggering of the TCR, formation of the IS initially involves reorganising the actin cytoskeleton towards the cell interface, followed by movement of TCR micro-clusters towards the centre of the IS (cSMAC). TSAd regulates chemokine induced T cell migration and actin polymerization via its interaction with Itk[18]. TSAd may influence specific NK cell immune responses, since www.nature.com/scientificreports/
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