Erika Scholz1, Anna Mestre-Ferrer1, Xavier Daura2, Noel García-Medel3, Montserrat Carrascal4, Eddie A James5, William W Kwok5, Francesc Canals6, Iñaki Álvarez7. 1. Institut de Biotecnologia i de Biomedicina and Universitat Autònoma de Barcelona, Bellaterra, Spain. 2. Institut de Biotecnologia i de Biomedicina and Universitat Autònoma de Barcelona, Bellaterra, Spain, and Catalan Institution for Research and Advanced Studies, Barcelona, Spain. 3. InnovativeHealth Group-Parque Científico de Madrid, Madrid, Spain. 4. CSIC/UAB Proteomics Laboratory, IIBB-CSIC/Institut d'Investigacions Biomèdiques August Pi i Sunyer, Bellaterra, Spain. 5. Benaroya Research Institute at Virginia Mason, Seattle, Washington. 6. Vall d'Hebron University Hospital Research Institute Proteomics Laboratory, Barcelona, Spain. 7. Institut de Biotecnologia i de Biomedicina and Universitat Autònoma de Barcelona, Bellaterra, Spain. Inaki.Alvarez@uab.es.
Abstract
OBJECTIVE: To evaluate similarity of the peptide repertoires bound to HLA-DR molecules that are differentially associated with rheumatoid arthritis (RA), and to define structural features of the shared peptides. METHODS: Peptide pools bound to HLA-DRB1*01:01, HLA-DRB1*04:01, and HLA-DRB1*10:01 (RA associated) and those bound to HLA-DRB1*15:01 (non-RA-associated) were purified and analyzed by liquid chromatography (LC) matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MS) and LC-ion-trap MS. Peptide pools from each allotype were compared in terms of size, protein origin, composition, and affinity (both theoretical and experimental with some peptides). Finally, 1 peptide sequenced from DR1, DR4, and DR10, but not from DR15, was modeled in complex with all 4 HLA-DRB1 molecules and HLA-DRB5*01:01. RESULTS: A total of 6,309 masses and 962 unique peptide sequences were compared. DR10 shared 29 peptides with DR1, 9 with DR4, and 1 with DR15; DR1 shared 6 peptides with DR4 and 9 with DR15; and DR4 and DR15 shared 4 peptides. The direct identification of peptide ligands indicated that DR1 and DR10 were the most similar molecules regarding the peptides that they could share. The peptides common to these molecules contained a high proportion of Leu at P4 and basic residues at P8 binding core positions. CONCLUSION: The degree of overlap between peptide repertoires associated with different HLA-DR molecules is low. The repertoires associated with DR1 and DR10 have the highest similarity among the molecules analyzed (∼10% overlap). Among the peptides shared between DR1 and DR10, a high proportion contained Leu(4) and basic residues at the P8 position of the binding core.
OBJECTIVE: To evaluate similarity of the peptide repertoires bound to HLA-DR molecules that are differentially associated with rheumatoid arthritis (RA), and to define structural features of the shared peptides. METHODS: Peptide pools bound to HLA-DRB1*01:01, HLA-DRB1*04:01, and HLA-DRB1*10:01 (RA associated) and those bound to HLA-DRB1*15:01 (non-RA-associated) were purified and analyzed by liquid chromatography (LC) matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MS) and LC-ion-trap MS. Peptide pools from each allotype were compared in terms of size, protein origin, composition, and affinity (both theoretical and experimental with some peptides). Finally, 1 peptide sequenced from DR1, DR4, and DR10, but not from DR15, was modeled in complex with all 4 HLA-DRB1 molecules and HLA-DRB5*01:01. RESULTS: A total of 6,309 masses and 962 unique peptide sequences were compared. DR10 shared 29 peptides with DR1, 9 with DR4, and 1 with DR15; DR1 shared 6 peptides with DR4 and 9 with DR15; and DR4 and DR15 shared 4 peptides. The direct identification of peptide ligands indicated that DR1 and DR10 were the most similar molecules regarding the peptides that they could share. The peptides common to these molecules contained a high proportion of Leu at P4 and basic residues at P8 binding core positions. CONCLUSION: The degree of overlap between peptide repertoires associated with different HLA-DR molecules is low. The repertoires associated with DR1 and DR10 have the highest similarity among the molecules analyzed (∼10% overlap). Among the peptides shared between DR1 and DR10, a high proportion contained Leu(4) and basic residues at the P8 position of the binding core.
Authors: Erika Margaret Scholz; Miguel Marcilla; Xavier Daura; David Arribas-Layton; Eddie A James; Iñaki Alvarez Journal: Front Immunol Date: 2017-08-21 Impact factor: 7.561
Authors: Lue Ping Zhao; George K Papadopoulos; William W Kwok; Bryan Xu; Matthew Kong; Antonis K Moustakas; George P Bondinas; Annelie Carlsson; Helena Elding-Larsson; Johnny Ludvigsson; Claude Marcus; Martina Persson; Ulf Samuelsson; Ruihan Wang; Chul-Woo Pyo; Wyatt C Nelson; Daniel E Geraghty; Åke Lernmark Journal: Diabetes Date: 2019-05-24 Impact factor: 9.461
Authors: Vincent van Drongelen; Bruna Miglioranza Scavuzzi; Sarah Veloso Nogueira; Frederick W Miller; Amr H Sawalha; Joseph Holoshitz Journal: Sci Rep Date: 2021-01-28 Impact factor: 4.379