Chemistry Reference
In-Depth Information
coreceptor has a polypeptide stalk connecting the glycoprotein to
the thymocyte surface and this domain carries
O
- glycans. Immature CD4
+
CD8
+
double-positive thymocytes bind major histocompatibility complex (MHC) class I
tetramers more avidly than mature CD8 single-positive thymocytes. The differen-
tial binding properties are mediated by a developmentally expressed sialyltransfer-
ase (ST3Gal-I) acting on the
O
-glycans. The appearance of CD8
The CD8
α
β
β
linked core 1
sialic acid on mature thymocytes leads to a decrease in CD8
- MHCI avidity and
this mechanism accounts for the regulation of binding of dimeric CD8 to MHCI.
The cluster designation ' CD ' nomenclature identifi es groups (clusters) of mono-
clonal antibody binding to lymphocyte cell surface molecules. CD8
α
β
α
β
refers to a
subpopulation of CD8 cells with an
T cell antigen receptor (TCR), which is a
lineage marker for subpopulations of T cells. Two distinct types of TCR exist,
defi ned as
α
β
by virtue of their disulfi de linked polypeptide chains (please
see Info Box in Chapter 27 for information on the CD system).
During the differentiation of crypt cells in the intestinal brush border the mem-
brane - associated proteins pro -sucrase-isomaltase and dipeptidyl peptidase IV are
targeted for apical location. These glycoproteins have both
N
- and
O
- glycans. Full
O
-glycosylation is mediated by the
N
-glycans and the subsequent polarized sorting
of these proteins to the apical membrane requires intact
O
- glycans. This example
demonstrates interrelated but distinct roles for
N
- and
O
- glycans and their process-
ing in brush border enzyme expression during intestinal cell differentiation.
Further details on embryogenesis and fertilization can be found in Chapter 24 .
Immune cell expression and response is strongly linked with
O
- glycosylation in
the immune system and is apparent at several levels (please see Figure 7.1 and
also Chapter 27, especially Figure 27.4, which shows competition between core 2
extension and core 1 sialylation). A regulatory function for T lymphocyte core 2
α
β
and
γ
δ
β
- 1,6 - N - acetylglucosaminyltransferase (C2GnT, see Table 7.2 for the structure of
core 2) in the peripheral immune system has been identifi ed. CD43 is the major
cell-surface glycoprotein and carries core 2
O
-glycan structures. It is an activation
antigen expressed on both CD4 and CD8 single-positive T lymphocytes. Down-
regulation of CD43 occurs in thymic positive, selection suggesting that the C2GnT
modulated expression of CD43 glycoforms is associated with thymic selection
events. Overexpression of C2GnT in transgenic mice led to impaired cell-cell
interaction of T lymphocytes isolated from these mice, thus illustrating a reduced
immune response.
7.3.2
-
O
- G lc NA c
β
The presence and biological activity of
β
-
O
-GlcNAc on proteins is mediated
through the action of the
-
O
- GlcNAc hexosamini-
dase acting in a cyclic manner and interacting with kinases and phosphatases
which phosphorylate the same or adjacent serine and threonine residues in
acceptor proteins. The nature of this interplay is complex and includes both same-
site and adjacent-site occupancy for GlcNAc and phosphate [5] . Demonstration of
β
-
O
- GlcNAc transferase and
β
