Identification of CDCA1-derived long peptides bearing both CD4+ and CD8+ T-cell epitopes: CDCA1-specific CD4+ T-cell immunity in cancer patients
Identification of CDCA1-derived long peptides bearing both CD4+ and CD8+ T-cell epitopes: CDCA1-specific CD4+ T-cell immunity in cancer patients
复制标题
鉴定携带 CD4 和 CD8 T 细胞表位的 CDCA1 衍生长肽：癌症患者中的 CDCA1 特异性 CD4 T 细胞免疫
DOI：
10.1002/ijc.28376
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发表时间：
2014
期刊：
影响因子：
6.4
通讯作者：
Nishimura Y
中科院分区：
文献类型：
--
作者：
Tomita Y;Yuno A;Tsukamoto H;Senju S;Yoshimura S;Osawa R;Kuroda Y;Hirayama M;Irie A;Hamada A;Jono H;Yoshida K;Tsunoda T;Kohrogi H;Yoshitake Y;Nakamura Y;Shinohara M;Nishimura Y
我们最近通过全基因组基因芯片分析和CDCA1来源的细胞毒性T淋巴细胞(CTL)表位鉴定了一种新的癌症-睾丸抗原，细胞分裂周期相关1(CDCA1)。在这项研究中，我们试图确定CDCA1衍生的长肽(LP)可以诱导CD4+辅助T(Th)细胞和CTL。我们结合最近开发的预测人类白细胞抗原II类结合多肽的计算机算法和由人类白细胞抗原A2(A*02：01)或人类白细胞抗原A24(A*24：02)提出的CDCA1来源的CTL表位序列来选择包含Th细胞表位和CTL表位的候选CDCA1-LP。我们研究了CDCA1-LPs的免疫原性和携带CTL表位的LPs在人体外和体内HLAI类转基因小鼠体内的交叉激发潜能。然后，我们用干扰素-γ酶联免疫斑点法分析了头颈癌患者接种CDCA1CTL表位多肽前后Th细胞对CDCA1的应答。我们鉴定了两个CDCA1-LP，CDCA139--LP和CDCA155-78-LP，它们包含Th细胞和CTL识别的自然加工表位。CDCA1-LPsin体外和体内交叉递呈诱导CDCA1特异性CTL。此外，CDCA1特异性Th细胞可增强CDCA1特异性CTL的诱导。此外，CDCA1-LPs短时刺激外周血单个核细胞(PBMC)后，HNC患者外周血中CDCA1特异性Th细胞反应率显著升高(CDCA139--LP，74%；CDCA155-78-LP，68%)，但在健康献血员中未检测到。这些结果首次证明了在HNC患者中存在CDCA1特异性Th细胞反应，并强调了CDCA1-LP可能用于CDCA1特异性Th细胞和CTL的增殖。
We recently identified a novel cancer‐testis antigen, cell division cycle associated 1 (CDCA1) using genome‐wide cDNA microarray analysis, and CDCA1‐derived cytotoxic T lymphocyte (CTL)‐epitopes. In this study, we attempted to identify CDCA1‐derived long peptides (LPs) that induce both CD4+helper T (Th) cells and CTLs. We combined information from a recently developed computer algorithm predicting HLA class II‐binding peptides with CDCA1‐derived CTL‐epitope sequences presented by HLA‐A2 (A*02:01) or HLA‐A24 (A*24:02) to select candidate CDCA1‐LPs encompassing both Th cell epitopes and CTL‐epitopes. We studied the immunogenicity of CDCA1‐LPs and the cross‐priming potential of LPs bearing CTL‐epitopes in both humanin vitroand HLA‐class I transgenic micein vivo. Then we analyzed the Th cell response to CDCA1 in head‐and‐neck cancer (HNC) patients before and after vaccination with a CDCA1‐derived CTL‐epitope peptide using IFN‐γ enzyme‐linked immunospot assays. We identified two CDCA1‐LPs, CDCA139–64‐LP and CDCA155–78‐LP, which encompass naturally processed epitopes recognized by Th cells and CTLs. CDCA1‐specific CTLs were induced through cross‐presentation of CDCA1‐LPsin vitroandin vivo. In addition, CDCA1‐specific Th cells enhanced induction of CDCA1‐specific CTLs. Furthermore, significant frequencies of CDCA1‐specific Th cell responses were detected after short‐termin vitrostimulation of peripheral blood mononuclear cells (PBMCs) with CDCA1‐LPs in HNC patients (CDCA139–64‐LP, 74%; CDCA155–78‐LP, 68%), but not in healthy donors. These are the first results demonstrating the presence of CDCA1‐specific Th cell responses in HNC patients and underline the possible utility of CDCA1‐LPs for propagation of both CDCA1‐specific Th cells and CTLs.