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预测和鉴定癌症睾丸抗原 CT23 中 HLA-A*0201 限制性表位。

Prediction and identification of HLA-A*0201-restricted epitopes from cancer testis antigen CT23.

机构信息

Department of Immunology, School of Basic Medicine Science, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China.

Department of Histology and Embryology, School of Basic Medicine Science, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China.

出版信息

Hum Vaccin Immunother. 2023 Dec 15;19(3):2293299. doi: 10.1080/21645515.2023.2293299.

DOI:10.1080/21645515.2023.2293299
PMID:38100550
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10730135/
Abstract

Cancer-testis antigen CT23 is a class of tumor-associated antigens (TAA) characterized by restricted expression in male germ cells and a variety of tumor tissues. Numerous studies have shown that CT23 is closely related to tumor cell viability, proliferation, metastasis and invasion. CT23 is immunogenic and can cause specific immune response in tumor patients. Therefore, it is considered to be one of the best target antigens for designing therapeutic tumor vaccines and T-cell-mediated tumor immunotherapy. In this study, we initially obtained seven HLA-A0201-restricted CT23 epitope candidate peptides through the T cell epitope prediction program. Subsequently, a T2 cell binding assay revealed the potential binding of all candidate peptides with HLA-A2 molecules. Notably, peptide P7 (ALLVLCYSI) exhibited the highest affinity, as evidenced by a fluorescence index (FI) of 2.19. Dendritic cells (DCs) loaded with CT23 candidate peptide can stimulate CD8T cell activation and proliferation, and compared with other candidate peptides, candidate peptide P7 is superior. The cytotoxic T lymphocytes (CTLs) stimulated by the peptide P7 had killing effect on tumor cells (HLA-A0201, CT23), but no killing effect on tumor cells (HLA-A*0201, CT23). The CTLs induced by the peptide P7 also had a specific killing effect on T2 cells bearing the peptide P7. In summary, our findings suggest that the CT23 peptide P7 (ALLVLCYSI) can induce immune responses and holds potential for tumor-specific CTL therapy.

摘要

癌-睾丸抗原 CT23 是一类肿瘤相关抗原(TAA),其特征在于在雄性生殖细胞和多种肿瘤组织中受限表达。大量研究表明,CT23 与肿瘤细胞活力、增殖、转移和侵袭密切相关。CT23 具有免疫原性,可在肿瘤患者中引起特异性免疫反应。因此,它被认为是设计治疗性肿瘤疫苗和 T 细胞介导的肿瘤免疫治疗的最佳靶抗原之一。在本研究中,我们最初通过 T 细胞表位预测程序获得了七个 HLA-A0201 限制性 CT23 表位候选肽。随后,T2 细胞结合测定显示所有候选肽均与 HLA-A2 分子具有潜在结合。值得注意的是,肽 P7(ALLVLCYSI)表现出最高的亲和力,荧光指数(FI)为 2.19。负载 CT23 候选肽的树突状细胞(DC)可刺激 CD8T 细胞的激活和增殖,与其他候选肽相比,候选肽 P7 具有优势。由肽 P7 刺激的细胞毒性 T 淋巴细胞(CTL)对肿瘤细胞(HLA-A0201,CT23)具有杀伤作用,但对不表达 HLA-A*0201,CT23 的肿瘤细胞没有杀伤作用。由肽 P7 诱导的 CTLs 对携带肽 P7 的 T2 细胞也具有特异性杀伤作用。综上所述,我们的研究结果表明,CT23 肽 P7(ALLVLCYSI)可诱导免疫反应,具有用于肿瘤特异性 CTL 治疗的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae1e/10730135/f9c17b67d16b/KHVI_A_2293299_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae1e/10730135/95d386ecf02e/KHVI_A_2293299_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae1e/10730135/c27d53a5eaab/KHVI_A_2293299_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae1e/10730135/e03cede0237f/KHVI_A_2293299_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae1e/10730135/83733bb05fe4/KHVI_A_2293299_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae1e/10730135/3e7859195ac2/KHVI_A_2293299_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae1e/10730135/0e40156c1f00/KHVI_A_2293299_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae1e/10730135/f9c17b67d16b/KHVI_A_2293299_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae1e/10730135/95d386ecf02e/KHVI_A_2293299_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae1e/10730135/c27d53a5eaab/KHVI_A_2293299_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae1e/10730135/e03cede0237f/KHVI_A_2293299_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae1e/10730135/83733bb05fe4/KHVI_A_2293299_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae1e/10730135/3e7859195ac2/KHVI_A_2293299_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae1e/10730135/0e40156c1f00/KHVI_A_2293299_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae1e/10730135/f9c17b67d16b/KHVI_A_2293299_F0007_OC.jpg

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