Identification of Two Lpp20 CD4(+) T Cell Epitopes in Helicobacter pylori-Infected Subjects.

Identification of Two Lpp20 CD4(+) T Cell Epitopes in Helicobacter pylori-Infected Subjects.
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幽门螺杆菌感染受试者中两个 Lpp20 CD4( ) T 细胞表位的鉴定

DOI:
10.3389/fmicb.2018.00884
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发表时间:
2018
影响因子:
5.2
通讯作者:
Li Y
Li Y
中科院分区:
生物学2区
文献类型:
--
作者:
Ning Y;Ye J;Wen J;Wu D;Chen Z;Lin Y;Hu B;Luo M;Luo J;Ning L;Li Y

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抗原特异性CD 4 + T细胞在针对幽门螺杆菌(H. pylori)感染。Lpp 20是H. pylori作为疫苗接种策略的主要保护性抗原之一。本研究在Lpp 20中发现了两个H-2d限制性CD 4 + T细胞表位,并构建了基于这些表位的表位疫苗。幽门感染免疫显性CD 4 + T细胞应答是抗病毒、抗菌和抗肿瘤细胞免疫的重要特征。然而,尽管H. pylori保护性抗原已被鉴定,免疫显性HLA限制性Lpp 20 CD 4 + T细胞表位尚未阐明。本研究采用系统的方法对H.幽门螺杆菌感染患者利用体外重组Lpp 20(rLpp 20)特异性扩增的H. pylori感染的受试者和27个18聚体重叠的合成肽跨越整个Lpp 20蛋白,我们已经表明L55-72和L79-96具有CD 4 + T细胞应答的优势表位。然后用各种延伸或截短的13肽筛选这两个18肽优势表位的核心序列。免疫显性表位定位于L57-69和L 83 -95。将具有不同HLA等位基因的各种EB病毒(EBV)转化的B淋巴母细胞样细胞系(B-LCL)用作抗原呈递细胞(APC)以将肽呈递给CD 4 + T细胞。用HLA类抗体封闭法确定限制性分子。L57-69受DRB 1 -1501限制,L 83 -95受DRB 1 -1602限制。表位在负载rLpp 20的自体树突状细胞(DC)上被识别,但也在用H. pylori(HP-WCL)的抗原表位,表明这些表位是由APC天然加工和呈递的。从H. pylori感染的患者,并用L57-69和L 83 -95刺激。这两个表位能够刺激CD 4 + T细胞增殖。本研究对潜在的H.幽门疫苗。
Antigen-specific CD4+ T cells play an essential role in effective immunity against Helicobacter pylori (H. pylori) infection. Lpp20, a conserved lipoprotein of H. pylori, has been investigated as one of major protective antigens for vaccination strategies. Our previous study identified two H-2d-restricted CD4+ T cell epitopes within Lpp20 and an epitope vaccine based on these epitopes was constructed, which protected mice in prophylactic and therapeutic vaccination against H. pylori infection. Immunodominant CD4+ T cell response is an important feature of antiviral, antibacterial, and antitumor cellular immunity. However, while many immunodominant HLA-restricted CD4+ T cell epitopes of H. pylori protective antigens have been identified, immunodominant HLA-restricted Lpp20 CD4+ T cell epitope has not been elucidated. In this study, a systematic method was used to comprehensively evaluate the immunodominant Lpp20-specific CD4+ T cell response in H. pylori-infected patients. Using in vitro recombinant Lpp20 (rLpp20)-specific expanded T cell lines from H. pylori-infected subjects and 27 18mer overlapping synthetic peptides spanned the whole Lpp20 protein, we have shown that L55–72 and L79–96 harbored dominant epitopes for CD4+ T cell responses. Then the core sequence within these two 18mer dominant epitopes was screened by various extended or truncated 13mer peptides. The immunodominant epitope was mapped to L57–69 and L83–95. Various Epstein-Barr virus (EBV) transformed B lymphoblastoid cell lines (B-LCLs) with different HLA alleles were used as antigen presenting cell (APC) to present peptides to CD4+ T cells. The restriction molecules were determined by HLA class-antibody blocking. L57–69 was restricted by DRB1-1501 and L83–95 by DRB1-1602. The epitopes were recognized on autologous dendritic cells (DCs) loaded with rLpp20 but also those pulsed with whole cell lysates of H. pylori (HP-WCL), suggesting that these epitopes are naturally processed and presented by APC. CD4+ T cells were isolated from H. pylori-infected patients and stimulated with L57–69 and L83–95. These two epitopes were able to stimulate CD4+ T cell proliferation. This study may be of value for the future development of potential H. pylori vaccine.
DOI: 10.1016/s1286-4579(03)00114-x
发表时间: 2003-07-01
影响因子: 5.8
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系统鉴定幽门螺杆菌感染个体中对 HpaA 的免疫显性 CD4 T 细胞反应。
DOI: 10.18632/oncotarget.11092
发表时间: 2016-08-23
期刊: Oncotarget
影响因子: --
作者:
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发表时间: 2011-05-31
影响因子: 11.1
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DOI: 10.1084/jem.188.12.2277
发表时间: 1998-12-21
期刊: The Journal of experimental medicine
影响因子: --
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