Loading of antigenic peptides

Stable Identifier
Reaction [transition]
Homo sapiens
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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).
Literature References
PubMed ID Title Journal Year
10064083 Identification of destabilizing residues in HLA class II-selected bacteriophage display libraries edited by HLA-DM

Sinigaglia, F, Kropshofer, H, Gallazzi, F, Sturniolo, T, Raddrizzani, L, Vogt, AB, Bono, E, Hammer, J, Hämmerling, GJ

Eur J Immunol 1999
8849454 Enhanced dissociation of HLA-DR-bound peptides in the presence of HLA-DM

Jensen, PE, Weber, DA, Evavold, BD

Science 1996
10631952 The impact of the non-classical MHC proteins HLA-DM and HLA-DO on loading of MHC class II molecules

Kropshofer, H, Vogt, AB, Hämmerling, GJ

Immunol Rev 1999
8145819 Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide

Gorga, JC, Jardetzky, TS, Urban, RG, Strominger, JL, Brown, JH, Stern, LJ, Wiley, DC

Nature 1994
8947036 Editing of the HLA-DR-peptide repertoire by HLA-DM

Moldenhauer, G, Kropshofer, H, Blum, JS, Vogt, AB, Hammer, J, Hämmerling, GJ

EMBO J 1996
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