immunological synapse
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IMMUNOLOGICAL
SYNAPSEPresented by Candice Churaman
Charles Okonkwo
Shawn Felix
An immunological synapse also known as a supramolecular
adhesion complex (SMAC) is the cell to cell contact between the T
cell, its co-receptors and the antigen presenting cell.
The site of contact is composed of concentric rings with each
containing segregated cluster of proteins :
Central supramolecular activation complex (cSMAC)
- comprises of the T cell receptor, it’s co-receptor (CD 4 or
CD 8), CD 28, CD 2 and PKC θ
Peripheral supramolecular activation complex (pSMAC)
- comprises of LFA1, ICAM-1 and talin
Distal supramolecular activation complex (dSMAC)
- enriched in CD 43, CD44 and CD 45
Enhancing signalling
Terminating signalling and/or effector function
Balancing signalling
Directing secretion
• The mechanism of immune synapse are: passive and
active.
• Passive is defined as: binding and steric factors.
(Čemerski and Shaw, 2006)
The diagram on the left shows the
mechanisms of redistribution and
segregation of molecules at the cell
surface.
Fig.1: The mechanisms involved in
synapse formation. (Čemerski and
Shaw, 2006)
Active Mechanism: This is the lateral movement on the surface
and polarised exocytosis of vesicular stores. (van der Merwe et
al., 2000)
There are various amounts of cell surface molecules which is
transported from the intracellular vesicular compartments to
the immune synapse. Examples of these are: FasL & CTLA-4.
(van der Merwe et al., 2000)Fig.2: The transportation of cell
surface molecules into the
intracellular vesicular compartments.
(van der Merwe et al., 2000)
IMMUNOLOGICAL SYNAPSE- Pathology : HIV as a case study
Model of virological and immunological synapse formation in the contribution to HIV persistence
Virological synapse (left panel) is mediated through interactions of gp41/gp1209(shown in red) on an HIV-infected CD4+T cell with CD4+ (brown) on the cell surface of an uninfected target CD4+ T cell.
Interactions are stabilized by ICAM-1(green) and LFA-1(blue) and takes place even in the presence of ART.
IS formation(right panel) initiated through interaction of MHC class II(green) on an APC and the TCR(red) of an Infected T cell may induce latency via inhibitory signals within the IS to reduce T-cell activation.
Trends in Immunological synapse
Then
Shows the contact region between
T-cells and APCs that forms upon
TCR stimulation with peptide –
MHC
In addition to naïve and effector T
cells, also found in other immune
system cells. Example: CTLs, NK
cells, NKTcells and B cells
A concentric bull’s eye structure
consisting of 3 sub regions: cSMAC,
pSMAC and DPC.
Now
TCR microclusters(MCs) containing
additional signalling molecules defined
as the minimal active signalling unit of
IS
Existence of kinapses, short lived
asymmetric synapses, in motile T cells.
Segregation of the cSMAC into two
distinct sub regions – a central, CD3high
region(signal termination) and an outer
CD3low annular ring enriched in CD28
and PKCθ,a site of sustained signalling.
Conclusion
IS involves reorganization of not only cell surface receptors, but also actin and
microtubule cytoskeletons leading to signalling and secretion
Further work elucidating a clear pathway that regulates centrosome movement within
immune cells is still required.
References :
J.C. Stinchcombe, G.M. Griffiths. The role of the secretory immunological
synapse in killing by CD8+ CTL. Semin. Immunol., 15 (2003), pp. 301–305
Colin L., Van Lint C. Molecular control of HIV-1 postintegration latency: implications
for the development of new therapeutic strategies. Retrovirology. 2009; 6:111.
PubMed.
Angus, K. and Griffiths, G. (2013). Cell polarisation and the
immunological synapse. Current Opinion in Cell Biology, 25(1),
pp.85-91.
Čemerski, S. and Shaw, A. (2006). Immune synapses in T-cell
activation. Current Opinion in Immunology, 18(3), pp.298-304.
Davis, D. and Dustin, M. (2004). What is the importance of the
immunological synapse?. Trends in Immunology, 25(6), pp.323-327.
Rodríguez-Fernández, J., Riol-Blanco, L. and Delgado-Martín, C.
(2010). What is an immunological synapse?. Microbes and
Infection, 12(6), pp.438-445.
Van der Merwe, P. (2002). Formation and function of the
immunological synapse. Current Opinion in Immunology, 14(3),
pp.293-298.
Van der Merwe, P., Davis, S., Shaw, A. and Dustin, M. (2000).
Cytoskeletal polarization and redistribution of cell-surface
molecules during T cell antigen recognition. Seminars in
Immunology, 12(1), pp.5-21.
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