Journal Article

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

Degenhardt, Frauke, Wendorff, Mareike, Østerbye, Thomas, Rosati, Elisa, Garcia Alvarez, Heli M., ElAbd, Hesham, Buus, Søren, Franke, Andre, Nielsen, Morten

2020

Overview

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.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Algorithms / Amino acids / Antigen Presentation / Autoimmune diseases / Binding Sites / CD4 antigen / CD4 Antigens - immunology / CD4 Antigens - metabolism / Cell-mediated immunity / Combined vaccines / Databases, Protein / Datasets / Disease / Epitopes / Epitopes, T-Lymphocyte - immunology / Epitopes, T-Lymphocyte - metabolism / High-Throughput Screening Assays / Histocompatibility antigen HLA / Histocompatibility Antigens Class II - immunology / Histocompatibility Antigens Class II - metabolism / HLA / HLA Antigens - immunology / HLA Antigens - metabolism / Humans / Immune response / Immunology / Learning algorithms / Ligands / Lymphocytes T / Machine Learning / Mass spectrometry / MHC class II / peptide binding / Peptides / prediction / Protein Array Analysis / Protein Binding / Protein Interaction Domains and Motifs / Proteins / Scientific imaging / ultra-high density peptide microarray / Vaccine development