Biology Reference
In-Depth Information
serves to contain the released lytic molecules at the target cell membrane (Beal
et al.
2008
). This may slow their inactivation and increase local concentration of
these molecules at the target cell surface (Millard et al.
1984
; Henkart et al.
1984
;
de Saint Basile et al.
2010
), enhancing the effectiveness of target cell lysis.
21.6 Conclusion
In conclusion, it seems likely that dynein plays a major role in the MTOC
translocation and secretory vesicle movements that result in localized secretion,
which lies at the heart of T cell effector functions. The signals that link TcR
ligation to activation events that trigger dynein movements appear to now have
been identified. Still there is much that is unknown. At present the way that PKC
and calcium might modulate dynein function are not known. Understanding how
these activities are regulated may help us understand some aspects of how tumor
cells avoid destruction by T cells.
Acknowledgments This work was supported by NIH grants to Y.S. (AI52812; CA131973) and
NIH 1 R21 AA15437-01A1 to M.P.
References
Andzelm MM et al (2007) Myosin IIA is required for cytolytic granule exocytosis in human NK
cells. J Exp Med 204(10):2285-2291
Anikeeva N et al (2005) Distinct role of lymphocyte function-associated antigen-1 in mediating
effective cytolytic activity by cytotoxic T lymphocytes. Proc Nat Acad Sci USA 102(18):6437-6442
Ardouin L et al (2003) Vav1 transduces TCR signals required for LFA-1 function and cell
polarization at the immunological synapse. Eur J Immunol 33(3):790-797
Avraham H et al (2000) RAFTK/Pyk2-mediated cellular signalling. Cell Signal 12(3):123-133
Banerjee PP et al (2007) Cdc42-interacting protein-4 functionally links actin and microtubule
networks at the cytolytic NK cell immunological synapse. J Exp Med 204(10):2305-2320
Beal AM et al (2009) Kinetics of early T cell receptor signaling regulate the pathway of lytic
granule delivery to the secretory domain. Immunity 31(4):632-642
Beal AM et al (2008) Protein kinase C theta regulates stability of the peripheral adhesion ring
junction
and
contributes
to
the
sensitivity
of
target
cell
lysis
by
CTL.
J
Immunol
181(7):4815-4824
Blanchard N, Di Bartolo V, Hivroz C (2002) In the immune synapse, ZAP-70 controls T cell
polarization and recruitment of signaling proteins but not formation of the synaptic pattern.
Immunity 17(4):389-399
Blott EJ, Griffiths GM (2002) Secretory lysosomes. Nat Rev Mol Cell Biol 3(2):122-131
Bossi G, Griffiths GM (2005) CTL secretory lysosomes: biogenesis and secretion of a harmful
organelle. Semin Immunol 17(1):87-94
Bunnell SC et al (2001) Dynamic actin polymerization drives T cell receptor-induced spreading:
a role for the signal transduction adaptor LAT. Immunity 14(3):315-329
Burkhardt JK et al (1993) Lytic granules from cytotoxic T cells exhibit kinesin-dependent
motility on microtubules in vitro. J Cell Sci 104(Pt 1):151-162
