Antigen Presenting Cells (APCs)
361
ivy or penicillins, that bind covalently to
proteins before or after take-up by APCs
and then can cause allergy.
3.2
Biochemical Nature of Antigens
APCs are able to successfully present a
large variety of organic substances (mainly
consisting of carbon, hydrogen, oxygen,
and nitrogen atoms); however, not a single
inorganic substance is known to be able
to trigger an antigen-speciFc immune
response
without
the
involvement
of
proteins. This is also true for large crystals,
such as renal calculi. This clear difference
in
the
immunogenicity
indicates
that
th
ead
ap
t
i
v
eimmun
es
y
s
t
eme
vo
l
v
edto
circumvent the danger originating from
organic and not inorganic material.
The most potent antigens are proteins
and polypeptides. This is also true for
polypeptides that consist of D-amino acids
instead of naturally occurring
L-amino
acids. The reason for the strong immunos-
timulatory capacity is that proteins are
easily recognized by the B-cell receptor
and by (soluble) antibodies in the blood
as well. In addition, proteins give rise
to peptides during processing by APCs
and peptides are the substances of choice
to activate cellular immune responses
through recognition by the T-cell receptor
of T lymphocytes (Table 2).
Polysaccharides and glycans are by far
weaker antigens than proteins. They can
activate B cells but not T cells because
APCs cannot present polysaccharides to
T cells. Nevertheless,
Saccharomyces gly-
can
stimulates macrophages to secrete IL-1
and TN±-
α
, thereby supporting antitumor
immunity in mice. Polysaccharides from
bacteria, such as multiple branched glu-
cose polymers (dextranes), induce strong
antibody responses in humans and mice,
however, not in rabbits or guinea pigs.
Most lipids are too small to act as
antigens that induce antibody production.
Similar to other low molecular weight
substances, a few lipids can function as
haptens, such as cardiolipin. Cardiolipin is
a phospholipid derived from the mitochon-
drial membrane. It is released from cells
upon bacterial infection with
Treponema
pallidum
, binds to carrier proteins and, in
this context, initiates formation of anticar-
diolipin antibodies (Table 2).
H
ow
e
v
e
r
,DC
ss
u
c
ha
sLC
se
x
p
r
e
s
s
CD1 molecules that bind and present
certain lipids or glycolipids in order to
induce
T-lymphocyte activation. Nong-
lycosylated and glycosylated mycolates,
Tab. 2
Antigens presented by APCs via MHC and CD1 molecules, versus
haptens.
Restriction
Antigen
Hapten
MHC class I/MHC class II
Proteins
Polysaccharides
Polypeptides
DNA
Peptides
Penicillin
Glycopeptides
Cardiolipin
CD1
Mycolates
Organic substances
Diacylglycerols
Sphingolipids
Polyisoprenoids
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