title: Arginine (Di)methylated Human Leukocyte Antigen Class I Peptides Are Favorably Presented by HLA-B*07.
abstract: Alterations in protein post-translational modification (PTM) are recognized hallmarks of diseases. These modifications potentially provide a unique source of disease-related human leukocyte antigen (HLA) class I-presented peptides that can elicit specific immune responses. While phosphorylated HLA peptides have already received attention, arginine methylated HLA class I peptide presentation has not been characterized in detail. In a human B-cell line we detected 149 HLA class I peptides harboring mono- and/or dimethylated arginine residues by mass spectrometry. A striking preference was observed in the presentation of arginine (di)methylated peptides for HLA-B*07 molecules, likely because the binding motifs of this allele resemble consensus sequences recognized by arginine methyl-transferases. Moreover, HLA-B*07-bound peptides preferentially harbored dimethylated groups at the P3 position, thus consecutively to the proline anchor residue. Such a proline-arginine sequence has been associated with the arginine methyl-transferases CARM1 and PRMT5. Making use of the specific neutral losses in fragmentation spectra, we found most of the peptides to be asymmetrically dimethylated, most likely by CARM1. These data expand our knowledge of the processing and presentation of arginine (di)methylated HLA class I peptides and demonstrate that these types of modified peptides can be presented for recognition by T-cells. HLA class I peptides with mono- and dimethylated arginine residues may therefore offer a novel target for immunotherapy.
authors: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Padualaan 8, 3584 CH Utrecht, The Netherlands.|Netherlands Proteomics Centre , Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors: Fabio
authors: F
authors: Marino
authors: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Padualaan 8, 3584 CH Utrecht, The Netherlands.|Netherlands Proteomics Centre , Padualaan 8, 3584 CH Utrecht, The Netherlands.|Institute for Translational Vaccinology , P.O. Box 450, 3720 AL Bilthoven, The Netherlands.
authors: Geert P M
authors: GP
authors: Mommen
authors: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Padualaan 8, 3584 CH Utrecht, The Netherlands.|Netherlands Proteomics Centre , Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors: Anita
authors: A
authors: Jeko
authors: Institute for Translational Vaccinology , P.O. Box 450, 3720 AL Bilthoven, The Netherlands.
authors: Hugo D
authors: HD
authors: Meiring
authors: Centre for Infectious Disease Control, National Institute for Public Health and the Environment , P.O. Box 1, 3720 BA Bilthoven, The Netherlands.
authors: Jacqueline A M
authors: JA
authors: van Gaans-van den Brink
authors: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Padualaan 8, 3584 CH Utrecht, The Netherlands.|Netherlands Proteomics Centre , Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors: Richard A
authors: RA
authors: Scheltema
authors: Centre for Infectious Disease Control, National Institute for Public Health and the Environment , P.O. Box 1, 3720 BA Bilthoven, The Netherlands.
authors: Cécile A C M
authors: CA
authors: van Els
authors: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Padualaan 8, 3584 CH Utrecht, The Netherlands.|Netherlands Proteomics Centre , Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors: Albert J R
authors: AJ
authors: Heck
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation; D001120:Arginine / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D001665:Binding Sites; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics* / Q000276:immunology; D002460:Cell Line; D015870:Gene Expression; D006162:Guanylate Cyclase / Q000235:genetics* / Q000276:immunology; D015793:HLA-B7 Antigen; D006801:Humans; D008745:Methylation; D010449:Peptide Mapping; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D011392:Proline / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000276:immunology
chemical_list: D053468:CARD Signaling Adaptor Proteins; C425023:HLA-B*07 antigen; D015793:HLA-B7 Antigen; D010455:Peptides; D001120:Arginine; D011392:Proline; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases; C426242:CARD11 protein, human; D006162:Guanylate Cyclase
keywords: ADMA; CARM1; EThcD; HLA class I; PRMT5; SDMA; arginine methylation