Kopicki, Janine-DeniseJanine-DeniseKopickiSaikia, AnkurAnkurSaikiaNiebling, StephanStephanNieblingGünther, ChristianChristianGüntherAnjanappa, RaghavendraRaghavendraAnjanappaGarcia-Alai, MariaMariaGarcia-AlaiSpringer, SebastianSebastianSpringerUetrecht, CharlotteCharlotteUetrecht2023-02-162023-02-162022https://dspace.ub.uni-siegen.de/handle/ubsi/2443Finanziert im Rahmen der DEAL-Verträge durch die Universitätsbibliothek SiegenAn essential element of adaptive immunity is selective binding of peptide antigens by major histocompatibility complex (MHC) class I proteins and their presentation to cytotoxic T lymphocytes. Using native mass spectrometry, we analyze the binding of peptides to an empty disulfide-stabilized HLA-A*02:01 molecule and, due to its unique stability, we determine binding affinities of complexes loaded with truncated or charge-reduced peptides. We find that the two anchor positions can be stabilized independently, and we further analyze the contribution of additional amino acid positions to the binding strength. As a complement to computational prediction tools, our method estimates binding strength of even low-affinity peptides to MHC class I complexes quickly and efficiently. It has huge potential to eliminate binding affinity biases and thus accelerate drug discovery in infectious diseases, autoimmunity, vaccine design, and cancer immunotherapy.enNamensnennung 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/610 Medizin, GesundheitHigh-throughput screeningMass spectrometryMHC class IMolecular biophysicsArticleMHC Klasse IHigh throughput screeningMassenspektrometriePeptid-Bindungurn:nbn:de:hbz:467-24432