Analyzing the effect of peptide-HLA-binding ability on the immunogenicity of potential CD8+ and CD4+ T cell epitopes in
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ORIGINAL ARTICLE
Analyzing the effect of peptide-HLA-binding ability on the immunogenicity of potential CD8+ and CD4+ T cell epitopes in a large dataset Shufeng Wang1 • Jintao Li1 • Xiaoling Chen1 • Li Wang1 • Wei Liu1 Yuzhang Wu1
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Ó Springer Science+Business Media New York 2016
Abstract Immunogenicity is a key factor that influences whether a peptide presented by major histocompatibility complex (MHC) can be a T cell epitope. However, peptide immunization experiments have shown that approximately half of MHC class I-binding peptides cannot elicit a T cell response, indicating the importance of analyzing the variables affecting the immunogenicity of MHC-binding peptides. In this study, we hierarchically investigated the contribution of the binding stability and affinity of peptide– MHC complexes to immunogenicity based on the available quantitative data. We found that the immunogenicity of peptides presented by human leukocyte antigen (HLA) class I molecules was still predictable using the experimental binding affinity, although approximately one-third of the peptides with a binding affinity stronger than 500 nM were non-immunogenic, whereas the immunogenicity of HLA-II-presented peptides was predicted well using the experimental affinity and even the predicted affinity. The positive correlation between the binding affinity and stability was only observed in peptide–HLA-I complexes with a binding affinity stronger than 500 nM, which suggested that the stability alone could not be used for the prediction of immunogenicity. A characterization and comparison of the ‘holes’ in the CD8? and CD4? T
Electronic supplementary material The online version of this article (doi:10.1007/s12026-016-8795-9) contains supplementary material, which is available to authorized users. & Shufeng Wang [email protected] & Yuzhang Wu [email protected] 1
Institute of Immunology PLA, Third Military Medical University, Chongqing 400038, China
cell repertoire provided an explanation for the observed differences between the immunogenicity of peptides presented by HLA class I and II molecules. We also provided the optimal affinity threshold for the potential CD4? and CD8? T cell epitopes. Our results provide important insights into the cellular immune response and the accurate prediction of T cell epitopes. Keywords Human leukocyte antigen (HLA) Immunogenicity Affinity Stability T cell repertoire
Introduction In the vertebrate immune system, T cell receptors (TCRs) recognize peptides presented by major histocompatibility complexes (MHCs) on the surface of antigen-presenting cells. Peptides that bind to the MHC molecule and trigger a cellular immune response are referred to as T cell epitopes, which are of great importance in the development of epitope-based vaccines and immunotherapies against viral infections, tumors and autoimmune diseases [1–4]. The binding of a peptide to a MHC molecule is a prerequisite to eliciting a cellular immune response. In the past few years, immunologists have put great efforts into identif
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