The immunological synapse is a specialized signaling structure formed at the interface between T lymphocytes and antigen presenting cells. It consists of three main components: T cell receptors, adhesion molecules, and co-stimulatory molecules. Formation of the mature immunological synapse involves molecular redistribution through diffusion and cytoskeletal movement over 5-30 minutes, resulting in a structure with central, peripheral, and distal supramolecular activation clusters that facilitate T cell signaling and activation. This signaling activates transcription factors that induce cytokine gene expression and T cell effector functions.

1. IMMUNOLOGICAL SYNAPSE
Presented by- Budha Ratna Rav

2. Meaning of Immunological synapse
Immunological synapse formation
Formation of mature immunological synapse
Mechanism of Synapse assembly formation
Molecular architecture of immunological synapse
Signaling through immunological synapse
Conclusion
Reference
Overview

3. Immunological synapse is specialized signaling area at
interface between T-lymphocytes and Antigen
presenting cells(APCs).
Immunological synapse have three main components:
1)T-cell receptor (TCR), Adhesion molecules and co-
stimulatory molecules.
Term given by M Norcross .
Activation of T-lymphocytes and secretes the cytokines
and chemokines.
Meaning of Immunological synapse:
Important properties of immunological synapse:
1) Cells remain individuals.
2) Adhesion.
3) Stability.
4) Directed secretions.

4. Immunological synapse formation
1)Interaction between T-lymphocyte and
APCs. This interaction is mediated by
Adhesion molecule LFA-1 on T-cell and
ICAM on APCs.
2)Upon conjugation of T-cell with APCs, T-
cell stop their migration.
3)After conjugation T-cell get polarized.

5. Molecular Redistribution to form mature immunological
synapse
1) Initially TCR-pMHC complexes accumulate at the
periphery of contact site between T-cell and pMHC
lipid bilayer.
2) Binding between LFA-1 & ICAM initially detected at
the center of contact.
This synapse formation is referred as pre-mature
synapse.
Within minutes after contact formation the molecule
pattern get reversed that structure is referred as mature
immunological synapse.
Formation of mature immunological synapse

6. Synapse assembly formation is achieved by two
mechanisms:
1) Diffusion: In resting condition intracellular
molecules are randomly laterally diffuses. Upon
conjugate formation with APC-diffusion
molecules are slowed or arrested in regions
where new interaction with immobile ligands.
2) Cytoskeletal driven movement: When T-cells
are treated with Cytochalasin-D , shows the
defects in formation of immunological synapse.
Defects in cytoskeletal components such as
Vau-1, Rac also shows the defects in
immunological formation.
Mechanism of Synapse assembly formation

7. Within 5-30 minutes after the productive
engagement of TCR a mature immunological
synapse is assembled. Kupfer described this
assembly as Supramolecular activation cluster
(SMAC).
SMAC contains the three components: cSMAC,
pSMAC, dSMAC.
cSMAC- Enriched in the TCRs, CD2, CD4/CD8
molecules.
pSMAC- Cell adhesion molecules are present such
as LFA1, Cytoskeletal linker talin.
dSMAC- Costimulatory molecules are present
such as CD43, CD45.
Molecular architecture of immunological synapse

8. Signaling through immunological synapse
TCR is a multimeric protein complex is made up of six different
subunits α, β, γ, δ, ε and ζ.
α, β heterodimer is responsible for the Antigen recognition.
CD3 chains (γ, δ, ε) and ζ homodimer for signal transduction.
TCR when engaged with pMHC-II, the cytoplasmic domains of
the CD3 subunits and ζ homodimer get phosphorylated by p56-
Lck and Fyn.
ZAP70 is activated by PTK, phosphorylation of TCR.
ZAP70 activate the LAT(Linker activation of T-cell) and
phosphorylated LAT serves as docking site for multiple adaptor
molecules that help in the expression of cytokine gene.
Activation of LAT activates the four different intracellular
transduction pathway for expression of cytokine gene.

9. Calcineurin pathway (Represent the signaling in violet color):
I) PLC- γ bids to the phosphorylated LAT via its SH2 domain
and is activated by phosphorylation of tyrosine residues by
ZAP70, Itk and Fyn.
II) Activated PLC hydrolyses phosphatidyl inositol 3-
phosphate into Inositol-3-phosphate (IP3) and DAG.
III) IP3 is released into cytoplasm and binds to own receptor
on ER membrane.
IV) Upon IP3 receptor binding, Ca2+ stores in ER released into
cytoplasm.
V) This initial increase in concentration of Ca2+ opens Ca2+
release activated channels at the plasma membrane leads
to the entry of Ca2+ ion into cytoplasm.
VI) Increase in the level of Ca2+, activate the protein
phosphatase calcineurin which turn to dephosphorylate
the transcription factor nuclear factor of T-cell (NFAT).
VII)NFAT enters in to the nucleus of T-cell and activate the
transcription of cytokine genes.

10. PKC-θ pathway:(Represents in orange
color)
i) After the hydrolysis of phosphatidyl
inositol 3- phosphate, The DAG remains
in the T-cell where it activates the
Serine/Threonine kinase PKC-θ.
ii) PKC-θ induce the phosphorylation and
consequent in ubiquitination of Ikβ.
iii)Ubiquitinated Ikβ is degraded by
proteasomes and release the transcription
factor NFkβ.
iv)NFkβ enters into the nucleus and activate
the transcription of cytokine gene.

11. Ras/ERK pathway (Green):
I) Phosphorylated LAT serves as docking site
for adopter molecule Grb2 that binds to the
Ras-GDP/GTP exchange factor.
II) After binding of Grb2 to Ras-GDP/GTP get
activated.
III)Ras activated the cascade of
serine/threonine kinase that leads to the
activation of MAP-kinase(Erk1/2).
IV)Erk1/2 activation leads to the expression of
Fos.
V) Fos helps in the expression of cytokine gene.

12. Conclusion
Immunological synapse has no specification in function
but is simply the manifestation of signal transmission
between APCs and T-cell.
IS play role in the activation of T-cell by which activated T-
cells shows the effect of cellular mode of immunity as well
as humoral immunity.

14. Reference