HLA class II immunopeptidomics reveals that co‐inherited HLA‐allotypes within an extended haplotype can improve proteome coverage for immunosurveillance. Issue 17 (17th August 2021)

• Record Type: Journal Article
• Authors: Ramarathinam, Sri H.; Ho, Bosco K.; Dudek, Nadine L.; Purcell, Anthony W.
• Other Names: Purcell Anthony W. guestEditor.; Ramarathinam Sri guestEditor.
• Is Part Of: Proteomics. Volume 21:Issue 17/18(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-08-17
• Subjects: C1R -- haplodome -- HLA class II -- immunopeptidomics -- MHC -- tissue typing; Proteins -- Separation -- Periodicals; Bioinformatics -- Periodicals; Proteomics -- Periodicals; Genomes -- Periodicals; Molecular genetics -- Periodicals; 572.605
• DOI: 10.1002/pmic.202000160
• Languages: English
• ISSNs: 1615-9853

Abstract

Abstract: Human leucocyte antigen (HLA) class II molecules in humans are encoded by three different loci, HLA‐DR, ‐DQ, and ‐DP. These molecules share approximately 70% sequence similarity and all present peptide ligands to circulating T cells. While the peptide repertoires of numerous HLA‐DR, ‐DQ, and ‐DP allotypes have been examined, there have been few reports on the combined repertoire of these co‐inherited molecules expressed in a single cell as an extended HLA haplotype. Here we describe the endogenous peptide repertoire of a human B lymphoblastoid cell line (C1R) expressing the class II haplotype HLA‐DR12/DQ7/DP4. We have identified 71350 unique naturally processed peptides presented collectively by HLA‐DR12, HLA‐DQ7, or HLA‐DP4. The resulting "haplodome" is complemented by the cellular proteome defined by standard LC‐MS/MS approaches. This large dataset has shed light on properties of these class II ligands especially the preference for membrane and extracellular source proteins. Our data also provides insights into the co‐evolution of these conserved haplotypes of closely linked and co‐inherited HLA molecules; which together increase sequence coverage of cellular proteins for immune surveillance with minimal overlap between each co‐inherited HLA‐class II allomorph.