Carbohydrate Antigens
297
Organization (W.H.O). Instead of large
capsular polysaccharides, its oligosaccha-
ride was conjugated with different protein
carriers for vaccinations. Age-related shift-
ing of antibody responses and Ig class
switching to the protective IgG isotypes
were observed with these vaccines, re-
sulting in better protection of high-risk
populations from
H. influenzae
B. Since
these conjugate vaccines have become
available, meningitis and other systemic
H. influenzae
B infections have virtually
disappeared. The principles underlying
the approaches to
H. influenzae
Bv
a
c
-
cines have been extended to microbial
polysaccharides of other bacteria, viruses,
parasites, and so on.
6
Future Prospects
Recognition of carbohydrates as antigens
began with the study of microbial polysac-
charides. In 1917, Dochez and Avery found
that when
Pneumococci
were grown in
fluid media, there was a substance in
the culture fluid that precipitated specif-
ically with antisera to the same
Pneumo-
coccus
. Heidelberger and Avery showed
that this substance was a polysaccha-
ride and not a protein, as previously
thought. In the past few decades, a large
amount of valuable information regarding
the structural and immunological prop-
erties of various classes of carbohydrate
antigens has been accumulated. In the
new millennium, this Feld faces serious
challenges as well as remarkable new
opportunities.
The
genome-sequencing
project
has
reached a conclusion that only about
30 000 genes in the human genome must
account for the complexity of the hu-
man organism. This Fnding emphasizes
the importance of posttranslational protein
modiFcations in modulating the biological
activities of proteins and their cellular
functions. Glycosylation is one of the most
important protein posttranslational mod-
iFcations, which introduces sugar chains
of various structures to a newly synthe-
sized protein molecule at given positions.
Unraveling the biological roles of carbo-
hydrate diversity attracts scientists from
many scientiFc disciplines. An interest-
ing analysis that appeared recently is
about the possible contribution of car-
bohydrate chains to the neural network
in the brain (Dr. Yoshitaka Nagai, Mit-
subishi Kagaku Institute of Life Sciences).
It is estimated that 10
4
synaptic con-
tacts are present for a single neuron.
The total number of neurons in a hu-
man brain is as large as 1
.
4
×
10
10
.The
information content of such a network
system in the brain is, thus, estimated
to be on the order of more than 10
14
.
This is far beyond the information car-
ried by the human genome at the DNA
sequence level, which is around the order
of 3
×
10
9
to 10
10
. Recent investigations
using gene-targeting technology were able
to generate animals with selective genetic
defect. ±or example, a single glycosyl-
transferase can be targeted and destroyed.
Several groups of scientists investigated
such genetically engineered animals by
all available means and from different
scientiFc aspects. They systematically in-
vestigated not only the tissue expression of
sugar chains but also the learning ability
and behavior of an animal. Evidences ob-
tained begin to suggest a link between
speciFc glycosyltransferase and certain
functional disorders in the brain. Per-
haps, such comprehensive investigation
reflects the characteristics of a new sci-
entiFc discipline – glycomics or systemic
glycobiology.
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