Polarity of CD4+ T cells towards the antigen presenting cell is regulated by the Lck adapter TSAd

Sci Rep. 2018 Sep 6;8(1):13319. doi: 10.1038/s41598-018-31510-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / immunology*
  • Animals
  • Antigen-Presenting Cells / cytology
  • Antigen-Presenting Cells / immunology*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / immunology
  • Cell Cycle Proteins
  • Cell Polarity / genetics
  • Cell Polarity / immunology*
  • Immunologic Memory*
  • Immunological Synapses / genetics
  • Immunological Synapses / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Microtubule-Organizing Center / immunology
  • Protein Kinase C-epsilon / genetics
  • Protein Kinase C-epsilon / immunology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Adhesion Molecules
  • Cell Cycle Proteins
  • Pard3 protein, mouse
  • Receptors, Antigen, T-Cell
  • Sh2d2a protein, mouse
  • Prkce protein, mouse
  • Protein Kinase C-epsilon