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.