Unbiased Characterization of Peptide-HLA Class II Interactions Based on Large-Scale Peptide Microarrays; Assessment of the Impact on HLA Class II Ligand and Epitope Prediction
Open Access
- 5 August 2020
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Immunology
- Vol. 11, 1705
- https://doi.org/10.3389/fimmu.2020.01705
Abstract
Human Leukocyte Antigen class II (HLA-II) molecules present peptides to T lymphocytes and play an important role in adaptive immune responses. Characterizing the binding specificity of single HLA-II molecules has profound impacts for understanding cellular immunity, identifying the cause of autoimmune diseases, for immunotherapeutics, and vaccine development. Here, novel high-density peptide microarray technology combined with machine learning techniques were used to address this task at an unprecedented level of high-throughput. Microarrays with over 200,000 defined peptides were assayed with four exemplary HLA-II molecules. Machine learning was applied to mine the signals. The comparison of identified binding motifs, and power for predicting eluted ligands and CD4+ epitope datasets to that obtained using NetMHCIIpan-3.2, confirmed a high quality of the chip readout. These results suggest that the proposed microarray technology offers a novel and unique platform for large-scale unbiased interrogation of peptide binding preferences of HLA-II molecules.Funding Information
- Deutsche Forschungsgemeinschaft (EXC 2167-390884018, RTG1743)
- Consejo Nacional de Investigaciones Científicas y Técnicas
- Agencia Nacional de Promoción Científica y Tecnológica (PICT-2016-0089)
- Danmarks Frie Forskningsfond (DFF - 6110-00644)
- Scleroseforeningen (A31444)
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