Tubulin and actin interplay at the T cell and antigen-presenting cell interface

Abstract

T cells reorganize their actin and tubulin-based cytoskeletons to provide a physical basis to the immune synapse. However, growing evidence shows that their roles on T cell activation are more dynamic than merely serving as tracks or scaffold for different molecules. The crosstalk between both skeletons may be important for the formation and movement of the lamella at the immunological synapse by increasing the adhesion of the T cell to the antigen-presenting cells (APC), thus favoring the transport of components toward the plasma membrane and in turn regulating the T-APC intercellular communication. Microtubules and F-actin appear to be essential for the transport of the different signaling microclusters along the membrane, therefore facilitating the propagation of the signal. Finally, they can also be important for regulating the endocytosis, recycling, and degradation of the T cell receptor signaling machinery, thus helping both to sustain the activated state and to switch it off.

Keywords: T cell; actin; immune synapse; microtubule-organizing centre.

Figure 1

Cytoskeletal dynamics at the Immunological synapse. TCR microclusters are formed upon activation by pMHC complexes, probably by fusion or apposition of pre-existing nanoclusters. Microclusters diffuse toward the center of the IS to form the cSMAC, where they are endocytosed and recycled. TCR activation promotes the reorganization of the cytoskeleton. Tubulin dynamics are favored by deacetylation of α-tubulin by HDAC6 and the MTOC re-orientates toward the APC through dynein/dynactin activity. The Golgi apparatus (GA) accompanies the MTOC. MVBs localize at the IS and facilitate massive polymerization of actin and exocytosis of exosomes at the immunological cleft. GA and MVBs provide the basis for polarized secretion. Mitochondria provide the energy for actomyosin contractile activity at the pSMAC. Cytoskeleton crosstalk at the IS may facilitate the movement of signaling microclusters.