![]() Moreover, presentation of peptides with proven T cell reactivity can be missed ( 2). LC-MS/MS analysis allows the identification of thousands of naturally presented peptides, but it is technically challenging and requires very large numbers of cells (i.e., 10 8 to 10 10) for good coverage ( 1, 2). However, they do not provide complete presentability landscapes across many HLAs. The main approaches used currently, analysis of MHC-eluted peptides by liquid chromatography with tandem mass spectrometry (LC-MS/MS) and in silico prediction algorithms, have contributed to the understanding of peptide presentation. Precise and comprehensive analysis of the short peptides presented by the major histocompatibility complex (MHC) molecules is therefore of major interest. We show that several mutations arising in viral strains expanding globally resulted in reduced peptide presentability by multiple HLA class II alleles, while some increased it, suggesting alteration of MHC II presentation landscapes as a possible immune escape mechanism.ĭecoding antigen presentation in the context of individual human leukocyte antigen (HLA) alleles is central for understanding immune homeostasis and protection from pathogens and underlies the design of immune medicines. Given the urgent need to understand immune evasion for formulating effective responses to threats such as SARS-CoV-2, we provide a comprehensive analysis of the presentability of all SARS-CoV-2 peptides in the context of several HLA class II alleles. Our platform provides a detailed picture by testing every antigen-derived peptide and is scalable to all the MHC II alleles. Here, we present MEDi, a novel mammalian epitope display that allows an unbiased, affordable, high-resolution mapping of MHC peptide presentation capacity. However, commonly used in silico predictions and mass spectroscopy have their limitations in precision, sensitivity, and throughput, particularly for MHC class II. Understanding peptide presentation by specific MHC alleles is fundamental for controlling physiological functions of T cells and harnessing them for therapeutic use. Joanna Swain, Conceptualization, Methodology, Project administration, Supervision, Writing - original draft, Writing - review & editing,Īnd Jan Kisielow, Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing Manfred Kopf, Methodology, Writing - review & editing, Katherine Triebel, Formal analysis, Investigation, Resources, Pooja Patel, Formal analysis, Investigation, Resources, Validation, Ohad Iosefson, Conceptualization, Data curation, Formal analysis, Methodology, Project administration, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing, ![]() ![]() Yannick Haldner, Investigation, Methodology, Writing - review & editing, Nastassja Cereghetti, Investigation, Validation, Lee, Investigation, Methodology, Validation, , † Sebastian Heer, Investigation, Validation, Franz-Josef Obermair, Conceptualization, Data curation, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing,įlorian Renoux, Investigation, Validation,
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