Research ArticleOriginal Article

Residue substitution enhances the immunogenicity of neoepitopes from gastric cancers

Huahui Yu, Jieyu Li, Yuan Yuan, Yu Chen, Jingwen Hong, Chunmei Ye, Wansong Lin, Huijing Chen, Zengqing Guo, Bo Li and Yunbin Ye
Cancer Biology & Medicine November 2021, 18 (4) 1053-1065; DOI: https://doi.org/10.20892/j.issn.2095-3941.2021.0022

Article Figures & Data

Figures

  • Figure 1
    Figure 1

    Flow chart of this study.

  • Figure 2
    Figure 2

    Affinity and stability detection of neoepitopes. (A) Affinity between different neoepitopes and HLA-A0201 molecules. Flow cytometry data are representative of 3 independent experiments. (B) Stability of different neoepitopes and HLA-0201 molecules after forming pMHC complexes. The dissociation rate was calculated as follows: dissociation rate = [mean PE fluorescence with given peptide (t = 0, 6, 12, 18, 24 h) – mean PE fluorescence without peptide (t = 0, 6, 12, 18, 24 h)]/[mean PE fluorescence with a given peptide (t = 0 h) – mean PE fluorescence without peptide (t = 0 h)]. Data represent the mean ± SD of 3 independent experiments.

  • Figure 3
    Figure 3

    The effect of different neoepitopes on T cells (A) IFN-γ secretion in T cells stimulated by dendritic cells (DCs) with different neoepitopes. Data represent the mean ± SD of 3 independent experiments. *P < 0.05; **P < 0.01; ***P < 0.001. (B) Proliferation of T cells stimulated by DCs with different neoepitopes. Flow cytometry data are representative of 3 independent experiments.

  • Figure 4
    Figure 4

    The cytotoxicity of neoepitope-specific cytotoxic T cells (CTLs) stimulated by wild-type and altered neoepitopes on target cells. (A) Comparison of the cytotoxicity of mutABCA2-specific CTLs and mutABCA2L2-specific CTLs on T2 cells loaded with mutABCA2. Data represent the mean ± SD of 3 independent experiments. (B) Comparison of the cytotoxicity of mutSP140-specific CTLs and mutSP140Y1-specific CTLs on T2 cells loaded with mutSP140. Data represent the mean ± SD of 3 independent experiments. (C) Comparison of the cytotoxicity of mutSTOM-specific CTLs and mutSTOML2-specific CTLs on T2 cells loaded with mutSTOM. Data represent the mean ± SD of 3 independent experiments.

  • Figure 5
    Figure 5

    Recognition and activation of neoepitope-specific cytotoxic T cells (CTLs) stimulated by wild-type neoepitopes and altered neoepitopes on T2 cells loaded with neoepitopes. (A) IFN-γ expression in wild-type neoepitope-specific CTLs and altered neoepitope-specific CTLs. Data represent the mean ± SD of 3 independent experiments. *P < 0.05; **P < 0.01; ***P < 0.001. (B) TNF-α expression in wild-type neoepitope-specific CTLs and altered neoepitope-specific CTLs. Data represent the mean ± SD of 3 independent experiments. *P < 0.05; **P < 0.01; ***P < 0.001. (C) Perforin expression in wild-type neoepitope-specific CTLs and altered neoepitope-specific CTLs. The flow cytometry data are representative of 3 independent experiments. Data represent the mean ± SD of 3 independent experiments.

Tables

  • Table 1

    Affinity prediction and detection results of wild-type neoepitopes and altered neoepitopes

    Position of peptideSequencesPrediction algorithms-IEDBFIaDC50b
    mutABCA2FIGITATVV3.73.32 ± 0.36<18 h
    mutABCA2L2FLGITATVV1.04.49 ± 0.42>18 h
    mutSP140PLLPVTCGV2.13.79 ± 0.50>24 h
    mutSP140Y1YLLPVTCGV0.25.20 ± 0.57>24 h
    mutSTOMSVIISVDGV4.64.27 ± 0.52<18 h
    mutSTOML2SLIISVDGV1.04.71 ± 0.41>18 h
    HIV-1 peptideILKEPVHGV1.84.76 ± 0.41>24 h

    aFI = (average PE fluorescence with the given peptide – average PE fluorescence without peptide)/(average PE fluorescence without peptide). bDC50 is defined as the time required for 50% dissociation of the pMHC complex stabilized at t = 0 h.

    Back to top

    In this issue

    Print
    Download PDF
    Email Article
    Citation Tools

    Jump to section

    Keywords