372
Antigen Presenting Cells (APCs)
immune response. In the case of such a
primary response, a subset of long-lived T
cells is generated that gives an accelerated
response upon seeing the same antigen for
the second time. These T cells are called
memory T cells
. Memory T cells differ in
several instances from naive T cells, but
like naive T cells they require activation
by professional APCs in order to become
effector T cells.
Finally, it has been shown that T cells
need to contact APCs continuously in
order to stay alive. This is accomplished
by the recognition of MHC-self-peptide or
MHC-foreign peptide complexes on the
surface of APCs.
7.1
Cell Adhesion Molecules
The migration of naive T cells through
lymph nodes and their initial contacts with
APCs depend on interactions that are not
antigen-speci±c, hence are independent
from MHC-peptide complexes. The initial
cell–cell contact between APCs and T
cells is controlled by an array of adhesion
molecules
on
the
surface
of
T
cells
that recognize a complementary array of
adhesion molecules on the surface of
an APC. The main classes of adhesion
molecules are the selectins, the integrins,
members
of
the
Ig
superfamily,
and
mucin-like molecules.
Selectins are particularly important for
the T cell homing into particular tissues.
For example, L-selectins on the T-cell sur-
face binds to addressins, such as CD34 or
MAdCAM-1, on vascular endothelial cells.
To
guide
naive
T
cells
to
DCs,
chemokines play a role: the chemokine
MIP-3
β
directs naive T cells and ma-
ture DCs into lymphoid tissues. More-
over, DCs in lymphoid tissues express
the chemokine SLC (secondary lymphoid
tissue
chemokine)
that
binds
to
the
chemokine receptor CCR7 expressed on
naive T cells. This event obviously rein-
forces the strength of successive T cell–DC
interactions mediated via integrins and
proteins of the Ig superfamily.
Integrins are heterodimeric cell surface
proteins, consisting of a large
α
-subunit
and a smaller
β
-subunit. There are several
subfamilies of integrins broadly de±ned
by their common
β
-chains. An important
integrin expressed mainly by T cells, but
also by macrophages, is LFA-1 (lymphocyte
function-associated antigen-1), an
α
L
β
2
integrin. LFA-1 mediates migration of
both naive and effector T cells out of
the blood and the initial contact with
DCs. Another integrin VLA-4 (very late
activation antigen-4), which is particularly
strongly expressed by activated effector
T cells, and the Ig family member CD2
function as substitutes for LFA-1. The
majority of cell surface adhesion molecules
being involved in T cell–APC interactions
a
r
em
em
b
e
r
so
ft
h
eI
gs
u
p
e
r
f
am
i
l
y
.
Three very similar intercellular adhesion
molecules (ICAM-1, ICAM-2, ICAM-3)
bind to the integrin LFA-1. ICAM-1 (CD54)
and ICAM-2 (CD102) are expressed on
APCs and on epithelia, whereas ICAM-
3 (CD50) is only expressed on T cells
and B cells. In addition to binding to
LFA-1, ICAM-3 has a high af±nity for
the lectin DC-SIGN (DC-speci±c ICAM-
3-grabbing nonintegrin; CD209), which
is only found on DCs. The ICAM-3/DC-
SIGN interaction appears to be exclusive to
the contact between naive T cells and DCs,
whereas CD2 binding to LFA-3 synergizes
with LFA-1 binding to ICAM-1 and ICAM-
2onalltypesofAPCs.
Importantly,
it
turned
out
that
the
strength of the LFA-1/ICAM interaction
of a naive T cell and an APC depends
onthetypeo
fMHC–pep
t
idecomp
lexes
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