374
Antigen Presenting Cells (APCs)
7.3
The Immunological Synapse
High-resolution confocal microscopy re-
vealed that the key molecules involved
in the formation of heterotypic junc-
tions between
APCs
and
T
cells are
reorganized
in
a
highly
characteristic
manner. This specialized junction that
results from cytoskeleton-driven cluster-
ing of MHC-peptide complexes, T-cell
receptor molecules, adhesion molecules,
and costimulators has been termed the
immunological synapse
. It is the close appo-
sition of two membranes and the peculiar
shape of the T cell that is reminiscent of
neurological synapses (Fig. 6).
The immunological synapse consists of
two concentric rings. In the center, pro-
teins of the so-called central supramolec-
ular activation cluster (c-SMAC), such as
the T-cell receptor (TCR), CD2, CD3, the
costimulator CD28, the protein kinases
lck, fyn, and PKC-
θ
cocluster on the
T-cell surface. Complementarily, MHC-
peptide complexes and the costimulator
CD80 have been described to cluster in
the c-SMAC zone of APCs. The c-SMAC
is surrounded by a second zone, the
peripheral supramolecular activation clus-
ter (p-SMAC). On T cells, the p-SMAC
contains the integrin LFA-1 and the cy-
toskeletal protein talin. Accordingly, the
adhesion molecule ICAM-1, known to be a
ligand of LFA-1, coalesces in the p-SMAC
of APCs.
The p-SMAC provides adhesive anchor-
ing of the T cell to the APC, whereas the
c-SMAC represents a protected zone for
sustained signaling via the TCR. Immuno-
logical synapses are maintained for at least
1 h. Outside the p-SMAC is a third area
containing proteins that are excluded from
the synapse, such as the mucin CD43 or
the phosphatase CD45. Exclusion of both
types of proteins from the T cell–APC
contact area is essential, as both molecules
are very large and would therefore prevent
MHC-peptide
CD86
ICAM-1
LFA-1
CD28
TCR
CD28
CD86
ICAM-1
LFA-1
p-SMAC
p-SMAC
c-SMAC
APC
CD45
CD43
CD45
CD43
T cell
Fig. 6
The immunological synapse between a T
cell and an APC. In the central zone (c-SMAC),
MHC-peptide complexes, costimulators, for
example, CD86, TCRs, and CD28 accumulate. In
the surrounding ring zone, termed p-SMAC, the
adhesion molecules ICAM-1 and LFA-1 are
found. Excluded are large molecules, for
example, CD43 and CD45.
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