11
Introduction
Figure 1.5: Similarities between the peptide loading mechanisms facilitated by MHC I and
MHC II molecules. Peptide loading occurs in different compartments for MHC I (ER) and MHC II
(endosomes-lysosomes) molecules, but key features of the peptide loading/editing process are similar, as
illustrated here. Empty MHC I molecules become part of a peptide-loading complex involving tapasin,
ERp57 and calreticulin; tapasin links the peptide loading complex to the peptide transporter TAP (not
shown). Tapasin is covalently linked to ERp57 and this hetero-dimer performs a peptide editing function.
Empty MHC I and MHC II molecules are highly unstable in the absence of peptide, and peptide loading
requires chaperones that stabilize the empty state in a functional form. In both cases, binding of high-
affinity peptides results in release from the respective chaperones. (Schulze and Wucherpfennig, 2012)
1.5
Structure of HLA-DM and lateral interaction with HLA-DR
As expected from the high overall sequence similarity (Cho et al., 1991; Kelly et al.,
1991) DM is a hetero-dimer with an overall fold and domain organization
similar to that
of classical MHC II molecules (Mosyak et al., 1998). The major difference compared to
MHC II molecules lies in the peptide-binding groove. The α helices of the α1 and ß1
domains of DM, which build the rim of the peptide-binding cleft for MHC II molecules,
are closer together and make several contacts which preclude peptide-binding (figure
1.6, A, C). At both ends of the cleft, bulky hydrophobic residues protrude into the