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Fig. 21.1 Steps in T cell activation. a T cell activation begins when the T cell receptor (TcR)
contacts antigen in the context of the major histocompatibility complex (MHC) of an antigen-
presenting cell (APC). b Signaling downstream of the TcR results in the formation of the
immunological synapse, which consists of several supramolecular activation clusters (SMACs).
The central SMAC (cSMAC) contains signaling molecules such as the TcR. The peripheral
SMAC (pSMAC) contains molecules such as the integrin LFA-1. Not shown is the distal SMAC
(dSMAC), which forms a ring around the pSMAC. In helper T cells and cytotoxic T lymphocytes
(CTLs) that kill their target slowly (c, d), the MTOC is thought to be translocated to the synapse
by dynein molecular motor anchored in a ring similar to the pSMAC (c). This is followed by
secretory vesicle transport by dynein toward the MTOC, where the vesicles are secreted (d). In
CTLs that perform fast target cell lysis (e, f), secretory vesicles are thought to be concentrated by
dynein around the MTOC before the MTOC is polarized (e). The MTOC is then translocated to
the synapse where the vesicles are secreted (f)
could reportedly involve kinesin and/or myosin-mediated transport of secretory
vesicles (Stinchcombe et al. 2001b ; Sanborn et al. 2011 ; Sanborn et al. 2009 ;
Andzelm et al. 2007 ; Kurowska et al. 2012 ; Burkhardt et al. 1993 ).
Understanding the processes of MTOC translocation has important medical
ramifications. Tumor cells can escape destruction by tumor-infiltrating CTLs,
despite the fact that these CTLs can be activated inside the tumor and can lyse
tumor cells outside the tumor environment. One of the reasons that tumor cells can
escape destruction is that something in the tumor environment blocks CTL MTOC
translocation and thus delivery of cytotoxic vesicles (Frey and Monu 2008 ; Koneru
et al. 2005 ; Monu and Frey 2007 ; Prevost-Blondel et al. 1998 ; Radoja et al. 2001 ).
It is possible that by understanding how this system works, we may be able to
detect exactly what fails in the tumor environment and then devise solutions to
prevent this from happening.
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