292
Carbohydrate Antigens
a wide variety of van der Waals and electro-
static interactions. The majority of crystal
structures so far resolved are associated
with a network of H-bonds, frequently
with water molecules, in their combin-
ing sites. Such bound water molecules
play important roles at the contacting in-
terface between carbohydrate ligands and
receptors. In addition, polyamphiphilic
surfaces were identiFed in the interfaces
of a number of carbohydrate ligand and
binding sites. The presence of relatively
rigid structures is required to produce
amphiphilic surfaces in solution. Carbo-
hydrate molecules with branched termini,
such as many blood group substances, are
favorable for the generation of such con-
tact surfaces.
4.2
Carbohydrate-based Self/nonself
Discrimination
In the higher eukaryotic species, carbo-
hydrate molecules serve as recognition
signals for the cell–cell communication
that occurs in a living organism. Carbohy-
drates also play critical roles in mediating
the interactions that occur between hosts
and microbes. This raises an important
question on how molecular and cellular
mechanisms allow self and nonself dis-
crimination on the basis of carbohydrate
structures. As discussed above, carbohy-
drates are unique in structural diversity.
The microbe-produced sugar chains are
structurally different from those expressed
by the host organisms and thereby rec-
ognized by the host immune system as
‘‘foreign’’ and elicit an antibody response.
This antibody or B-lymphocyte-mediated
machinery is specialized for immune de-
fense. It is, however, no longer useful for
cell–cell communication in a host since
B-cell clones that produce self-reactive
antibodies
are
generally
prohibited
in
the development of an individual’s im-
mune system. The lectin-mediated recog-
nition machinery plays important roles in
cell–cell communication.
Some
characteristic
differences
be-
tween the lectin-mediated and antibody-
mediated model of carbohydrate-recogni-
tion have been identiFed. ±irst, lectins
seem to have lower binding afFnity to
carbohydrates than antibodies do. Second,
most lectins recognize the terminal epi-
topes or terminal branches of carbohydrate
antigens; antibodies are able to bind either
the terminal or internal epitopes. Third,
lectins recognize a speciFc pattern, such
as clusters of sugar structures. Their se-
lectivity in carbohydrate binding is heavily
dependent on the topological distribution
of carbohydrate ligands. By contrast, anti-
body binding to carbohydrates is generally
less dependent on the topological distribu-
tion of sugar epitopes but strongly relies
on its binding afFnity. The so-called cluster
effect is seen in many lectin–carbohydrate
interactions in cellular systems. In fact,
the genetic and molecular machineries
for constructing high afFnity antibody-
combining sites are not present in lectin
systems. Apparently, the two carbohydrate-
recognition systems have evolved to be
better suited for their respective cellu-
lar functions.
In invertebrates and many lower ver-
tebrate species, there are no acquired
immune systems, such as those including
B-cells and T-cells as found in mam-
mals. They depend on the innate immune
systems to combat potential microbial
pathogens.
In
fact,
both
invertebrates
and vertebrates have a self/nonself pat-
tern recognition innate immunity system,
which is based on the detection of car-
bohydrates that decorate the surface of
microbial pathogen. This machinery is
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