PMID- 27503676 OWN - NLM STAT- MEDLINE DCOM- 20171016 LR - 20180403 IS - 1535-3907 (Electronic) IS - 1535-3893 (Linking) VI - 16 IP - 1 DP - 2017 Jan 6 TI - Arginine (Di)methylated Human Leukocyte Antigen Class I Peptides Are Favorably Presented by HLA-B*07. PG - 34-44 LID - 10.1021/acs.jproteome.6b00528 [doi] AB - 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. FAU - Marino, Fabio AU - Marino F AD - 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. AD - Netherlands Proteomics Centre , Padualaan 8, 3584 CH Utrecht, The Netherlands. FAU - Mommen, Geert P M AU - Mommen GP AD - 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. AD - Netherlands Proteomics Centre , Padualaan 8, 3584 CH Utrecht, The Netherlands. AD - Institute for Translational Vaccinology , P.O. Box 450, 3720 AL Bilthoven, The Netherlands. FAU - Jeko, Anita AU - Jeko A AD - 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. AD - Netherlands Proteomics Centre , Padualaan 8, 3584 CH Utrecht, The Netherlands. FAU - Meiring, Hugo D AU - Meiring HD AD - Institute for Translational Vaccinology , P.O. Box 450, 3720 AL Bilthoven, The Netherlands. FAU - van Gaans-van den Brink, Jacqueline A M AU - van Gaans-van den Brink JA AD - Centre for Infectious Disease Control, National Institute for Public Health and the Environment , P.O. Box 1, 3720 BA Bilthoven, The Netherlands. FAU - Scheltema, Richard A AU - Scheltema RA AD - 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. AD - Netherlands Proteomics Centre , Padualaan 8, 3584 CH Utrecht, The Netherlands. FAU - van Els, Cecile A C M AU - van Els CA AD - Centre for Infectious Disease Control, National Institute for Public Health and the Environment , P.O. Box 1, 3720 BA Bilthoven, The Netherlands. FAU - Heck, Albert J R AU - Heck AJ AD - 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. AD - Netherlands Proteomics Centre , Padualaan 8, 3584 CH Utrecht, The Netherlands. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160825 PL - United States TA - J Proteome Res JT - Journal of proteome research JID - 101128775 RN - 0 (CARD Signaling Adaptor Proteins) RN - 0 (HLA-B*07 antigen) RN - 0 (HLA-B7 Antigen) RN - 0 (Peptides) RN - 94ZLA3W45F (Arginine) RN - 9DLQ4CIU6V (Proline) RN - EC 2.1.1.319 (PRMT5 protein, human) RN - EC 2.1.1.319 (Protein-Arginine N-Methyltransferases) RN - EC 4.6.1.2 (CARD11 protein, human) RN - EC 4.6.1.2 (Guanylate Cyclase) SB - IM MH - Amino Acid Sequence MH - *Antigen Presentation MH - Arginine/immunology/*metabolism MH - B-Lymphocytes/cytology/immunology/*metabolism MH - Binding Sites MH - CARD Signaling Adaptor Proteins/*genetics/immunology MH - Cell Line MH - Gene Expression MH - Guanylate Cyclase/*genetics/immunology MH - HLA-B7 Antigen MH - Humans MH - Methylation MH - Peptide Mapping MH - Peptides/*chemistry/genetics/immunology MH - Proline/immunology/metabolism MH - Protein Binding MH - *Protein Processing, Post-Translational MH - Protein-Arginine N-Methyltransferases/genetics/immunology OTO - NOTNLM OT - ADMA OT - CARM1 OT - EThcD OT - HLA class I OT - PRMT5 OT - SDMA OT - arginine methylation EDAT- 2016/08/10 06:00 MHDA- 2017/10/17 06:00 CRDT- 2016/08/10 06:00 PHST- 2016/08/10 06:00 [pubmed] PHST- 2017/10/17 06:00 [medline] PHST- 2016/08/10 06:00 [entrez] AID - 10.1021/acs.jproteome.6b00528 [doi] PST - ppublish SO - J Proteome Res. 2017 Jan 6;16(1):34-44. doi: 10.1021/acs.jproteome.6b00528. Epub 2016 Aug 25.