Antigen Discovery and Specification of Immunodominance Hierarchies for MHCII-Restricted Epitopes
| Autor: | Daniel B. Graham, Jennifer G. Abelin, Daniel J. O’Connell, Kara L. Conway, Chengwei Luo, Moran Yassour, Guadalupe J. Jasso, Steven A. Carr, Mukund Varma, Caline G Matar, Eric M. Brown, Ariel Lefkovith, Ramnik J. Xavier |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Proteomics Antigenicity Receptors Antigen T-Cell Epitopes T-Lymphocyte Computational biology Immunodominance Biology medicine.disease_cause General Biochemistry Genetics and Molecular Biology Epitope Article Autoimmunity 03 medical and health sciences Immune system Antigen Single-cell analysis medicine Humans Amino Acid Sequence Antigen Presentation Immunodominant Epitopes T-cell receptor Histocompatibility Antigens Class II High-Throughput Nucleotide Sequencing General Medicine Listeria monocytogenes 030104 developmental biology Single-Cell Analysis |
| Popis: | Identifying immunodominant T cell epitopes remains a significant challenge in the context of infectious disease, autoimmunity, and immuno-oncology. To address the challenge of antigen discovery, we developed a quantitative proteomic approach that enabled unbiased identification of major histocompatibility complex class II (MHCII)-associated peptide epitopes and biochemical features of antigenicity. On the basis of these data, we trained a deep neural network model for genome-scale predictions of immunodominant MHCII-restricted epitopes. We named this model bacteria originated T cell antigen (BOTA) predictor. In validation studies, BOTA accurately predicted novel CD4 T cell epitopes derived from the model pathogen Listeria monocytogenes and the commensal microorganism Muribaculum intestinale. To conclusively define immunodominant T cell epitopes predicted by BOTA, we developed a high-throughput approach to screen DNA-encoded peptide-MHCII libraries for functional recognition by T cell receptors identified from single-cell RNA sequencing. Collectively, these studies provide a framework for defining the immunodominance landscape across a broad range of immune pathologies. |
| Databáze: | OpenAIRE |
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