Systematic identification of immunodominant CD4+ T cell responses to HpaA in<i>Helicobacter pylori</i>infected individuals

Hu, Jian; Chen, Li; Yang, Wenzhong; Li, Bin; Sun, Hongling; Wei, Shanshan; He, Yang; Zhao, Zhuo; Yang, Shi‐Ming; Zou, Quanming; Chen, Weisan; Guo, Hong; Wu, Chao

doi:10.18632/oncotarget.11092

Cited by 9 publications

(12 citation statements)

References 38 publications

(46 reference statements)

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“…Although some previous studies on H. pylori -specific Th1 cell responses focused on specific antigens, they did not identify individual epitopes and therefore were not aware of the influence of involved HLA (D'Elios et al, 1997b , 2003 ). Recently, many scientists began to pay attention to identifying HLA-restricted CD4 + T cell epitopes of H. pylori protective antigens using overlapping synthetic peptides, such as UreB 373−385 and UreB 438−452 (Yang et al, 2013 ), HpaA 88−100 and HpaA 142−159 (Chen et al, 2013 ; Hu et al, 2016 ). Chen et al found that the HpaA 88−100 -specific Th1-polarized response in H. pylori -infected subjects was linked with resistance to severe H. pylori- associated gastric diseases (Chen et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

“…Although several immunodominant epitopes of H. pylori protective antigens were identified (Chen et al, 2013 ; Yang et al, 2013 ; Li et al, 2015 ; Hu et al, 2016 ), much remains unclear concerning CD4 + T cell response to many H. pylori antigens. Our previous studies constructed an epitope vaccine based on our identified two Lpp20 H-2 d restricted CD4 + T cell epitopes (Li et al, 2012 ), which stimulated prophylactic and therapeutic responses with Th1-type profile against H. pylori in mice (Li et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

“…Many scientists in the vaccine field think that immunodominant CD4 + T cell epitopes seem to be critical for H. pylori vaccine development (Ermak et al, 1998 ; Akhiani et al, 2002 ; Nyström and Svennerholm, 2007 ). Although several immunodominant epitopes of H. pylori protective antigens were identified (Chen et al, 2013 ; Yang et al, 2013 ; Hu et al, 2016 ), few are known to immunodominant epitope-specific CD4 + T cells response of other H. pylori antigen and immunodominant CD4 + T cell epitope has yet to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

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

Ning

Wen

et al. 2018

Front. Microbiol.

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Ning

Wen

et al. 2018

Front. Microbiol.

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“…Several groups investigated Helicobacter vaccines using mouse models, however, very few tested their protective efficacy. The most commonly investigated vaccine antigens were urease B, neuraminyllactose‐binding hemagglutinin (HpaA), and H. pylori whole cells or lysates …”

Section: Vaccinesmentioning

confidence: 99%

“…[41][42][43] Several groups investigated Helicobacter vaccines using mouse models, however, very few tested their protective efficacy. The most commonly investigated vaccine antigens were urease B, 44,45 neuraminyllactose-binding hemagglutinin (HpaA), [46][47][48] and H. pylori whole cells or lysates. 49,50 Several different adjuvants were used in the published studies, but as in previous years, the most common was cholera toxin B subunit.…”

Section: Immunization and Vaccinesmentioning

confidence: 99%

Helicobacter: Inflammation, immunology and vaccines

2017

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Helicobacter pylori is usually acquired in early childhood and the infection persists lifelong without causing symptoms. In a small of cases, the infection leads to gastric or duodenal ulcer disease, or gastric cancer. Why disease occurs in these individuals remains unclear, however the host response is known to play a very important part. Understanding the mechanisms involved in maintaining control over the immune and inflammatory response is therefore extremely important. Vaccines against H. pylori have remained elusive but are desperately needed for the prevention of gastric carcinogenesis. This review focuses on research findings which may prove useful in the development of prognostic tests for gastric cancer development, therapeutic agents to control immunopathology, and effective vaccines.

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Design, implementation, and outcomes of an elective course on preliminary structural biology for undergraduate students majoring in biotechnology

Zhang

Jing

Luo

et al. 2019

Biochem Molecular Bio Educ

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Biotechnological pharmaceuticals is a key course offered to third‐year undergraduates majoring in biotechnology in our university. However, students often experience difficulties in understanding the principles of related technologies. In this study, we developed and implemented an elective course on preliminary structural biology for biotechnology undergraduates, aiming at reinforcing the principles of these technologies by experimental practice. The course was composed of three phases and lasted for 15 weeks, 18 students were randomly divided into six teams and were encouraged to design, prepare, carry out, and conclude a project on their own. The main contents of their project were cloning, expression, purification, and crystal screening of HpaA, a lipoprotein from the gastric pathogen Helicobacter pylori. Examination scores of biotechnology pharmaceuticals were used to assess learning outcomes. The results showed that students who participated in this course gained higher scores in the final examination, and they performed better on the questions specifically related to the elective course. These results demonstrated that the course enhanced students' understanding of the technologies involved in this course by practical applications. Thus, this elective course was effective in helping biotechnology undergraduates to learn the theory and application of biological technologies, and the experience gained in this course may be useful for other technology‐based courses.

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Systematic identification of immunodominant CD4+ T cell responses to HpaA inHelicobacter pyloriinfected individuals

Cited by 9 publications

References 38 publications

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

Helicobacter: Inflammation, immunology and vaccines

Design, implementation, and outcomes of an elective course on preliminary structural biology for undergraduate students majoring in biotechnology

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