T cell epitope spectrum of alpha-fetoprotein restricted by dominant HLA-A molecules in Chinese population
10.3760/cma.j.cn112309-20240628-00234
- VernacularTitle:中国人群优势HLA-A分子限制性甲胎蛋白T细胞表位谱研究
- Author:
Song YANG
1
;
Suyue ZHU
;
Yi WU
;
Wanliang SUN
;
Zhong LIU
;
Chuanlai SHEN
;
Zheng LU
Author Information
1. 蚌埠医科大学第一附属医院肝胆胰外科，蚌埠 233000
- Keywords:
Hepatocellular carcinoma;
Alpha-fetoprotein;
T cell epitope;
Human leukocyte antigen A;
Antigen-specific T cell
- From:
Chinese Journal of Microbiology and Immunology
2024;44(9):752-761
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate T cell epitope spectrum of alpha fetoprotein (AFP) restricted by 13 dominant human leukocyte antigen A (HLA-A) molecules in Chinese population.Methods:AFP T cell epitope candidates presented by 13 HLA-A molecules were in silico predicted using multiple epitope prediction algorithms. Then, the candidate epitope peptides were co-cultured in vitro with fresh peripheral blood mononuclear cells (PBMCs) from hepatocellular carcinoma (HCC) patients, followed by intracellular cytokine staining (ICS) and flow cytometry to verify the immunogenicity of the candidate epitope peptides. Peptide competition binding assay of HLA-A molecules were performed using 12 HMy2.CIR cell lines expressing the indicated HLA-A molecules to analyze the affinity and cross-restriction of candidate epitope peptides with HLA-A molecules. Results:PBMCs from 67 AFP + HCC patients were co-cultured in vitro with 42 candidate T cell epitope peptides, and the result showed that 20 epitope peptides stimulated CD8 + T cell responses (named as positive epitope peptides). Peptide competitive binding assay revealed 22 candidate epitope peptides with high affinity, 13 with inter affinity, six with low affinity, and 10 without affinity with indicated HLA-A molecules, respectively. The 20 positive epitope peptides presented high or inter affinity with corresponding HLA-A molecules and most of them displayed cross-binding properties with several HLA-A molecules. Conclusions:Twenty AFP-specific CD8 + T cell epitope peptides restricted by the predominant HLA-A molecules in Chinese population are obtained by the HCC patients-derived T-cell functional experiments, and the cross-binding ability of these epitope peptides to the corresponding HLA-A molecules is preliminary identified. These results provide systematic and fundamental data for the design of AFP-specific T cell detection systems and T cell epitope-based vaccines universal for the Chinese population.
