In the acidic compartments of MIICs the empty MHC II molecules are protected from unfolding and degradation by HLA-DM (DM). DM acts as a peptide editor, favouring the formation and presentation of long-lived MHC II peptide complexes on the surface of APCs. The intrinsic stability of a ligand determines whether a peptide is resistant or sensitive to DM-mediated release (Kropshofer et al. 1996, Weber et al. 1996). From X-ray structure analysis it is known that two types of forces contribute to the intrinsic stability of class II-peptide complexes: i) interactions of the anchor side chains of the peptides with specificity pockets of polymorphic residues of the peptide binding groove of MHC II and ii) hydrogen bonds between the peptide backbone and conserved residues of the peptide binding grooves (Stern et al. 1994, Kropshofer et al. 1999). Naturally-processed antigenic peptides 14-16 residues in length with many anchor residues and few destabilizing residues (glycine and proline) at non-anchor positions are the most resistant to DM-mediated release (Radrizzani et al. 1999, Kropshofer et al. 1999).