On the feasibility of mining CD8+ T cell receptor patterns underlying immunogenic peptide recognition

• DOI: 10.1007/s00251-017-1023-5
• Publication Date: 2017-08-04T01:43:14Z
• Authors: Nicolas De Neuter; Wout Bittremieux; Charlie Beirnaert; Bart Cuypers; Aida Mrzic; Pieter Moris; Arvid Suls; Viggo Van Tendeloo; Benson Ogunjimi; Kris Laukens; Pieter Meysman
• Keywords: Receptors, Antigen, T-Cell; Antigen-Presenting Cells; Epitopes, T-Lymphocyte; CD8-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes/immunology; Major Histocompatibility Complex; HIV-1/immunology; Random forest classifier; Antigen-Presenting Cells/immunology; Humans; Amino Acid Sequence; Antigen Presentation/immunology; Biology; Epitopes, T-Lymphocyte/immunology; Computer. Automation; Antigen Presentation; Amino Acid Sequence/genetics; Protein Binding/immunology; Immunoinformatics; Major Histocompatibility Complex/immunology; bioinformatics; 3. Good health; T cell epitope prediction; Peptides/immunology; Receptors, Antigen, T-Cell/immunology; HIV-1; Human medicine; T cell receptor; Peptides; Protein Binding

Abstract:Current T-cell epitope prediction tools are a valuable resource in designing targeted immunogenicity experiments. They typically focus on, and are able to, accurately predict peptide binding and presentation by major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells. However, recognition of the peptide-MHC complex by a T-cell receptor is often not included in these tools. We developed a classification approach based on random forest classifiers to predict recognition of a peptide by a T-cell and discover patterns that contribute to recognition. We considered two approaches to solve this problem: (1) distinguishing between two sets of T-cell receptors that each bind to a known peptide and (2) retrieving T-cell receptors that bind to a given peptide from a large pool of T-cell receptors. Evaluation of the models on two HIV-1, B*08-restricted epitopes reveals good performance and hints towards structural CDR3 features that can determine peptide immunogenicity. These results are of particularly importance as they show that prediction of T-cell epitope and T-cell epitope recognition based on sequence data is a feasible approach. In addition, the validity of our models not only serves as a proof of concept for the prediction of immunogenic T-cell epitopes but also paves the way for more general and high performing models.