Major histocompatibility complex (MHC) genes are highly polymorphic, which makes each MHC molecule different regarding their peptide repertoire, so they can bind and present to T lymphocytes. The increasing importance of immunopeptidomics and its use in personalized medicine in different fields such as oncology or autoimmunity demand the correct analysis of the peptide repertoires bound to human leukocyte antigen type 1 (HLA-I) and HLA-II molecules. Purification of the peptide pool by affinity chromatography and individual peptide sequencing using mass spectrometry techniques is the standard protocol to define the binding motifs of the different MHC-I and MHC-II molecules.
View Article and Find Full Text PDFObjective: 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).
Unlabelled: The thymus is the organ in which T lymphocytes mature. Thymocytes undergo exhaustive selection processes that require interactions between the TCRs and peptide-HLA complexes on thymus antigen-presenting cells. The thymic peptide repertoire associated with HLA molecules must mirror the peptidome that mature T cells will encounter at the periphery, including peptides that arise from tissue-restricted antigens.
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