Analyzing the effect of peptide-HLA-binding ability on the immunogenicity of potential CD8+ and CD4+ T cell epitopes in a large dataset.
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.
Institute of Immunology PLA, Third Military Medical University, Chongqing, 400038, China. wangshufeng81@hotmail.com.
Shufeng
S
Wang
Institute of Immunology PLA, Third Military Medical University, Chongqing, 400038, China.
Jintao
J
Li
Institute of Immunology PLA, Third Military Medical University, Chongqing, 400038, China.
Xiaoling
X
Chen
Institute of Immunology PLA, Third Military Medical University, Chongqing, 400038, China.
Li
L
Wang
Institute of Immunology PLA, Third Military Medical University, Chongqing, 400038, China.
Wei
W
Liu
Institute of Immunology PLA, Third Military Medical University, Chongqing, 400038, China. wuyuzhang@yahoo.com.
Yuzhang
Y
Wu
D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D066264:Datasets as Topic; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D006680:HLA Antigens / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D011485:Protein Binding
D000941:Antigens; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens
Affinity; Human leukocyte antigen (HLA); Immunogenicity; Stability; T cell repertoire