Abstract
In silico T-cell epitope prediction plays an important role in immunization experimental design and vaccine preparation. Currently, most epitope prediction research focuses on peptide processing and presentation, e.g., proteasomal cleavage, transporter associated with antigen processing (TAP), and major histocompatibility complex (MHC) combination. To date, however, the mechanism for the immunogenicity of epitopes remains unclear. It is generally agreed upon that T-cell immunogenicity may be influenced by the foreignness, accessibility, molecular weight, molecular structure, molecular conformation, chemical properties, and physical properties of target peptides to different degrees. In this work, we tried to combine these factors. Firstly, we collected significant experimental HLA-I T-cell immunogenic peptide data, as well as the potential immunogenic amino acid properties. Several characteristics were extracted, including the amino acid physicochemical property of the epitope sequence, peptide entropy, eluted ligand likelihood percentile rank (EL rank(%)) score, and frequency score for an immunogenic peptide. Subsequently, a random forest classifier for T-cell immunogenic HLA-I presenting antigen epitopes and neoantigens was constructed. The classification results for the antigen epitopes outperformed the previous research (the optimal AUC = 0.81, external validation data set AUC = 0.77). As mutational epitopes generated by the coding region contain only the alterations of one or two amino acids, we assume that these characteristics might also be applied to the classification of the endogenic mutational neoepitopes also called “neoantigens.” Based on mutation information and sequence-related amino acid characteristics, a prediction model of a neoantigen was established as well (the optimal AUC = 0.78). Further, an easy-to-use web-based tool “INeo-Epp” was developed for the prediction of human immunogenic antigen epitopes and neoantigen epitopes.
Highlights
An antigen consists of several epitopes, which can be recognized either by B- or T-cells and/or molecules of the host immune system
HLA-I antigen peptides are processed and presented as follows: (a) cytosolic and nuclear proteins are cleaved to short peptides by intracellular proteinases; (b) some are selectively transferred to the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP) transporter, and subsequently are treated by endoplasmic reticulum aminopeptidase; and (c) antigen-presenting cells (APCs) present peptides containing 8-11 AA residues on HLA class I
In our study, based on HLA-I T-cell peptides collected from experimentally validated antigen epitopes and neoantigen epitopes, we aim to build a novel method to further reduce the range of immunogenic epitope screening based on predicted p-major histocompatibility complex (MHC)
Summary
An antigen consists of several epitopes, which can be recognized either by B- or T-cells and/or molecules of the host immune system. Usually only a small number of amino acid residues that comprise a specific epitope are necessary to elicit an immune response [1]. The properties of these amino acid residues causing immunogenicity are unknown. Researchers can simulate antigen processing and presentation by computational methods to predict binding peptide-MHC complexes (pMHC). The cycle for vaccine development and immunization research is extended. We aim to develop a T-cell HLA class-I immunogenicity prediction method to further identify real epitopes/neoepitopes from p-MHC to shorten this cycle
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
