Arginine (di)methylated Human Leukocyte Antigen class I peptides are favorably presented by HLA-B*07

ABSTRACT: Specific alterations in protein post-translational modification (PTMs) are recognized hallmarks of diseases. These modifications potentially provide a unique disease-related source of Human Leukocyte Antigen (HLA) class I-presented peptide antigens that can elicit specific immune responses. Although, phosphorylated HLA peptides have received already some attention, the frequency and characteristics of arginine methylated HLA class I peptide presentation have not been explored in detail. In a model human B-cell line we detected by mass spectrometry (MS) 149 HLA class I peptides harboring mono- and/or di-methylated arginine residues. The source proteins of these antigens play important roles in signal transduction, gene transcription and DNA repair. A striking preference was observed in presentation of arginine (di)methylated peptides predicted to bind HLA-B*07 molecules, most likely because the binding motifs of this allele resemble the substrates for arginine methyl-transferases. The HLA-B*07 peptides were preferentially di-methylated at the P3 position in the sequence, thus consecutively to the proline anchor residue at position P2. Such a proline-arginine sequnce has been associated with the arginine methyl-transferases CARM1 and PRMT5. Making use of the specific neutral losses in the MS/MS spectra we could further assign most of the peptides to be asymmetrically di-methylated, most likely by CARM1. The here presented data expand our knowledge of processing and presentation of arginine (di)methylated HLA class I peptides, indicating that this type of modification is frequently presented for recognition by T-cells and might thus present a potential target for immunotherapy.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Fabio Marino  

LAB HEAD: Albert J.R. Heck

PROVIDER: PXD004233 | Pride | 2016-08-15

REPOSITORIES: Pride