Identification of destabilizing residues in HLA class II-selected bacteriophage display libraries edited by HLA-DM

• Verfasst von: Raddrizzani, Laura [VerfasserIn]
• Verfasst von: Kropshofer, Harald [VerfasserIn]
• Verfasst von: Hämmerling, Günter J. [VerfasserIn]
• Titel: Identification of destabilizing residues in HLA class II-selected bacteriophage display libraries edited by HLA-DM
• Verf.angabe: Laura Raddrizzani, Elisa Bono, Anne B. Vogt, Harald Kropshofer, Fabio Gallazzi, Tiziana Sturniolo, Günter J. Hämmerling, Francesco Sinigaglia and Juergen Hammer
• E-Jahr: 2006
• Jahr: 28 March 2006
• Jahr des Originals: 1999
• Umfang: 9 S.
• Fussnoten: First published: 28 March 2006 ; Elektronische Reproduktion der Druck-Ausgabe ; Gesehen am 16.02.2021
• Titel Quelle: Enthalten in: European journal of immunology
• Ort Quelle: Weinheim : Wiley-VCH, 1971
• Jahr Quelle: 1999
• Band/Heft Quelle: 29(1999), 2, Seite 660-668
• ISSN Quelle: 1521-4141
• DOI: doi:10.1002/(SICI)1521-4141(199902)29:02<660::AID-IMMU660>3.0.CO;2-I
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: HLA-DM
• Sach-SW: HLA-DR
• Sach-SW: Peptide binding
• Sach-SW: Peptide editing
• Sach-SW: Phage display
• K10plus-PPN: 1748435140

Abstract

HLA-DM (DM) functions as a peptide editor by catalyzing the release of class II-associated invariant chain peptides (CLIP) and other unstable peptides, thus supporting the formation of stable class II-peptide complexes for presentation. To investigate the general features that determine the DM susceptibility of HLA-DR1/peptide complexes, we generated a large DM-ensitive peptide repertoire from an M13 bacteriophage display library using a novel double selection protocol: we selected bacteriophage capable of binding to DR1 molecules and, subsequently, we enriched DR1-bound bacteriophage susceptible to elution by purified DM molecules. Sequence and mutational analyses of the DR1/DM double-selected peptides revealed that the amino acids Gly and Pro play a destabilizing role in the dissociation kinetics of DR1 ligands. This observation was confirmed also in natural peptide sequences such as CLIP 89 - 101, HA 307 - 319 and bovine collagen II (CII) 261-273. Our results demonstrate that DM susceptibility does not only depend on the number and nature of anchor residues, or the peptide length. Instead, less obvious sequence characteristics play a major role in the DM editing process and ultimately in the composition of peptide repertoires presented to T cells.