Immunologic Research

, Volume 64, Issue 4, pp 908–918 | Cite as

Analyzing the effect of peptide-HLA-binding ability on the immunogenicity of potential CD8+ and CD4+ T cell epitopes in a large dataset

  • Shufeng WangEmail author
  • Jintao Li
  • Xiaoling Chen
  • Li Wang
  • Wei Liu
  • Yuzhang WuEmail author
Original Article


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 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.


Human leukocyte antigen (HLA) Immunogenicity Affinity Stability T cell repertoire 



The study was supported by the Major Research Plan of the National Natural Science Foundation of China [91442203 to W.Y.] and that National Natural Science Foundation of China [31470899 to W.S.].

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

12026_2016_8795_MOESM1_ESM.docx (1 mb)
Supplementary material 1 (DOCX 1028 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Institute of Immunology PLAThird Military Medical UniversityChongqingChina

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