364
Antigen Presenting Cells (APCs)
reaches APCs, which take up and process
the antigen and present it to T lymphocytes
in the PP or in mesenteric lymph nodes.
4.4
Antigen Uptake in the Respiratory Tract
In the upper respiratory tract, antigen pre-
senting LCs occur in the transitional zones
between the keratinizing epithelium of the
skin and the mucosal surface of the nasal
cavity and the nasopharyngeal region, for
example, the lips. Moreover, APCs fulFll
their sentinel function in and around the
lymphoid tissue of Waldeyer’s ring. The
epithelium above the ring of Waldeyer con-
tains, just as BALT and GALT do, antigen
transporting M cells. ±urthermore, DCs
are found in the epithelium of the trachea.
The rest of the mucosal surface of the
upper respiratory tract serves to exclude
rather than take up antigen.
Antigen exclusion is also dominant in
the lower respiratory tract, in particu-
lar, the lung. Antigen clearance mainly
depends on mucociliary activity of the
epithelia and/or alveolar macrophages.
Macrophages in the alveoli act as both
phagocytic cells of the innate defense sys-
tem and as APCs giving rise to acquired
immunity. Some of them simply phagocy-
tose and digest foreign antigens involving
the lung; others stimulate a local im-
mune response. ±or this purpose, alveolar
macrophages loaded with antigen cross the
lining of the alveoli and migrate into lymph
nodes located in the lung tissue. Thus, sim-
ilar to DCs, alveolar macrophages form a
lung-speciFc antigen handling system.
5
Antigen Presenting Molecules
Both types of the classical molecules of
the MHC, class I and class II, are peptide
receptors
and
encoded
by
genes
that
display the highest degree of polymor-
phism in the genome. Within the MHC
molecules, the polymorphism is mainly
restricted to the regions that constitute
the antigenic peptide-binding cleft. The
advantage of the multitude of MHC alle-
les encoding for a multitude of distinct
peptide-binding speciFcities is that there
will be hardly any foreign peptide that
cannot be bound by at least a few indi-
viduals of a population. In contrast, CD1
molecules are MHC class I–like recep-
tors for mycobacterial lipids or glycolipids.
They are not encoded in the MHC and are
monomorphic. Their physiological role is,
as yet, ill deFned.
5.1
MHC Class I Molecules
MHC
class
I
molecules
are
glycosy-
lated transmembrane proteins that con-
sist
of
two
subunits:
the
larger
α
-
chain
encoded
in
the
MHC
genetic
locus
is
polymorphic
and
forms
the
peptide-binding site. It associates with
the
smaller
subunit,
β
2
-microglobulin
(
β
2m
), which is nonpolymorphic and en-
coded outside the MHC.
β
2m
and the
membrane-proximal
α
3
-domain
of
the
α
-chain
fold
as
immunoglobulin
do-
mains, whereas the membrane-proximal
(membrane-distal)
α
1
-and
α
2
-domain con-
stitute the peptide-binding cleft (±ig. 4).
Quite in contrast to other peptide re-
ceptors described in the hormone system,
the binding cleft of MHC molecules is
highly promiscuous so that a large vari-
ety of antigenic peptides can be presented.
In the case of MHC class I molecules,
this peculiarity is accomplished through
three structural criteria shared by peptide
ligands: (1) the peptide length is limited
to 8 to 10 amino acids, with the majority
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