336
P. M. RUDD et al.
B-microglobulin the fully assembled MHC is released from calnexin and binds
calreticulin, also through the terminal glucose residue. This event, which also
involves tapasin, is necessary for the loading of antigenic peptide from the TAP
transporter (Sadasivan et aI., 1996).
Membrane bound CD8 is a glycoprotein which stabilises the interaction of the
TCR with the human MHC molecule (HLA) class 1 carrying antigenic peptide.
CD8 binds to peptide loaded HLA class 1 molecules, interfacing with the a2 and
a3 domains of HLA-A2 and also contacting B2-microglobulin (Gao et al., 1997).
HLA B270S, prepared from the EBV transformed homozygous B-celliine LG-2,
contains a very restricted set of glycans (Rudd, P.M., Pazmany, 1., Strominger, J.L.
and Dwek, R.A.- unpublished data) and this is consistent with the analysis of a
set ofB27 molecules analysed by (Barber et al., 1996). The predominant structure
at Thr 86 was the fully galactosylated biantennary complex glycan containing
bisecting GlcNAc and core fucose, (shown in the fully sialylated form in Fig.
23.2). The N-linked sugars occupying the seven potential glycosylation sites on
the aB TCR complex and the site on CD8 have not yet been analysed, but in order
to demonstrate the extensive glycosylation of the interaction the proteins have
been modelled with bi-antennary complex glycans at each potential glycosylation
site (Fig 23.9).
9
Concluding Remarks
One of the essential elements of immunity is the recognition of foreign structures. Often, as in bacteria, the epitopes which interact with our immune system
are mutiply presented oligosaccharides which activate the complement pathway
both through the classical and the alternative pathways. Oligosaccharide recognition (e.g. by selectins) is also essential for the functioning of immune cells for
this event initiates the recruitment of cells to inflamed endothelial cells prior to
margination and extravasation. Here we have discussed the structures and functions of the oligosaccharides attached to effector or control molecules of the
immune system. The roles of the sugars include maintaining the 3D structure
and function of immunoglobulins and protection of proteins from proteolysis.
Oligo saccharides are also associated with particular autoimmune diseases, and
we have discussed the finding that specific glycoforms of IgG interact with MBL
and activate the complement pathway, suggesting a role for glycosylation in the
pathogenesis of RA. In complement control proteins such as CDS9 and DAF, the
attached oligosaccharides are important for the spatial orientation and function
of the molecules. Spatial orientation of proteins by their attached sugars is also a
factor in the intermolecular interactions between T-cells and antigen presenting
cells, in particular those involving the cell adhesion molecules, CD2 and CD48.
Finally the sugars attached to the MHC playa role in protein assembly and in the
formation of the complex required for the transfer of antigenic peptide to the
binding groove of the MHC.
P. M. RUDD et al.
B-microglobulin the fully assembled MHC is released from calnexin and binds
calreticulin, also through the terminal glucose residue. This event, which also
involves tapasin, is necessary for the loading of antigenic peptide from the TAP
transporter (Sadasivan et aI., 1996).
Membrane bound CD8 is a glycoprotein which stabilises the interaction of the
TCR with the human MHC molecule (HLA) class 1 carrying antigenic peptide.
CD8 binds to peptide loaded HLA class 1 molecules, interfacing with the a2 and
a3 domains of HLA-A2 and also contacting B2-microglobulin (Gao et al., 1997).
HLA B270S, prepared from the EBV transformed homozygous B-celliine LG-2,
contains a very restricted set of glycans (Rudd, P.M., Pazmany, 1., Strominger, J.L.
and Dwek, R.A.- unpublished data) and this is consistent with the analysis of a
set ofB27 molecules analysed by (Barber et al., 1996). The predominant structure
at Thr 86 was the fully galactosylated biantennary complex glycan containing
bisecting GlcNAc and core fucose, (shown in the fully sialylated form in Fig.
23.2). The N-linked sugars occupying the seven potential glycosylation sites on
the aB TCR complex and the site on CD8 have not yet been analysed, but in order
to demonstrate the extensive glycosylation of the interaction the proteins have
been modelled with bi-antennary complex glycans at each potential glycosylation
site (Fig 23.9).
9
Concluding Remarks
One of the essential elements of immunity is the recognition of foreign structures. Often, as in bacteria, the epitopes which interact with our immune system
are mutiply presented oligosaccharides which activate the complement pathway
both through the classical and the alternative pathways. Oligosaccharide recognition (e.g. by selectins) is also essential for the functioning of immune cells for
this event initiates the recruitment of cells to inflamed endothelial cells prior to
margination and extravasation. Here we have discussed the structures and functions of the oligosaccharides attached to effector or control molecules of the
immune system. The roles of the sugars include maintaining the 3D structure
and function of immunoglobulins and protection of proteins from proteolysis.
Oligo saccharides are also associated with particular autoimmune diseases, and
we have discussed the finding that specific glycoforms of IgG interact with MBL
and activate the complement pathway, suggesting a role for glycosylation in the
pathogenesis of RA. In complement control proteins such as CDS9 and DAF, the
attached oligosaccharides are important for the spatial orientation and function
of the molecules. Spatial orientation of proteins by their attached sugars is also a
factor in the intermolecular interactions between T-cells and antigen presenting
cells, in particular those involving the cell adhesion molecules, CD2 and CD48.
Finally the sugars attached to the MHC playa role in protein assembly and in the
formation of the complex required for the transfer of antigenic peptide to the
binding groove of the MHC.