A Comparative Analysis of the Peptide Repertoires of HLA–DR Molecules Differentially Associated With Rheumatoid Arthritis. Issue 10 (28th September 2016)

• Record Type: Journal Article
• Authors: Scholz, Erika; Mestre‐Ferrer, Anna; Daura, Xavier; García‐Medel, Noel; Carrascal, Montserrat; James, Eddie A.; Kwok, William W.; Canals, Francesc; Álvarez, Iñaki
• Is Part Of: Arthritis & rheumatology. Volume 68:Issue 10(2016)
• Page Start: 2412
• Page End: 2421
• Publication Date: 2016-09-28
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; 616.72
• DOI: 10.1002/art.39736
• Languages: English
• ISSNs: 2326-5191

Abstract

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.