A Dominant CD4+ T-Cell Response to Helicobacter pylori Reduces Risk for Gastric Disease in Humans

Chen, Li; Li, Bin; Yang, Wenzhong; He, Jialin; Li, Ningyi; Hu, Jian; He, Yang; Yu, Seung Do; Zhao, Zhuo; Luo, Ping; Zhang, Jinyong; Li, Hai–Bo; Zeng, Ming; Lu, Dongshui; Li, Bo–Sheng; Guo, Hong; Yang, Shi‐Ming; Guo, Gang; Mao, Xuhu; Chen, Weisan; Wu, Chao; Zou, Quanming

doi:10.1053/j.gastro.2012.12.002

Cited by 35 publications

(53 citation statements)

References 35 publications

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“…Pan-anti-DR (L243), anti-DP (B7/21), and anti-DQ (SPV-L3) antibodies were used as culture supernatants (14). Anti-rVV RNA-binding protein antibody TW2.3 (15) and anti-HA antibody H28-E23 (16) were kind gifts from Jonathan Yewdell and Jack Bennink (National Institutes of Health, Bethesda, MD).…”

Section: Methodsmentioning

confidence: 99%

“…Two milliliters of RF-10 with 20 U/ml recombinant human interleukin 2 (rIL-2) (Peprotech, Brisbane, Australia) were then added, and the cell lines were cultured in the rIL-2 containing RF-10 until use. Peptide-specific CD4 ϩ T cell lines were generated as previously described (14). In brief, PBMCs (1 ϫ 10 6 to 2 ϫ 10 6 ) were pulsed with 5 M peptide and cultured in 1 ml RP-5, consisting of RPMI 1640 (Gibco) supplemented with 5% human AB serum, L-glutamine (2 mM), 2-ME (5 ϫ 10 5 mM), and antibiotics (100 U/ml penicillin and 100 g/ml streptomycin) in 48-well tissue culture plates.…”

Section: Methodsmentioning

confidence: 99%

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Immunodominant CD4⁺T-Cell Responses to Influenza A Virus in Healthy Individuals Focus on Matrix 1 and Nucleoprotein

Chen

Zanker

Xiao

et al. 2014

J Virol

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Antigen-specific CD4؉ T cells are essential for effective virus-specific host responses, with recent human challenge studies (in volunteers) establishing their importance for influenza A virus (IAV)-specific immunity. However, while many IAV CD4 ؉ T cell epitopes have been identified, few are known to stimulate immunodominant CD4 ؉ T cell responses. Moreover, much remains unclear concerning the major antigen(s) responded to by the human CD4 ؉ T cells and the extents and magnitudes of these responses. We initiated a systematic screen of immunodominant CD4 ؉ T cell responses to IAV in healthy individuals. Using in vitro expanded-multispecificity IAV-specific T cell lines and individual IAV protein antigens produced by recombinant vaccinia viruses, we found that the internal matrix protein 1 (M1) and nucleoprotein (NP) were the immunodominant targets of CD4 ؉ T cell responses. Ten epitopes derived from M1 and NP were definitively characterized. Furthermore, epitope sequence conservation analysis established that immunodominance correlated with an increased frequency of mutations, reflecting the fact that these prominent epitopes are under greater selective pressure. Such evidence that particular CD4 ؉ T cells are important for protection/recovery is of value for the development of novel IAV vaccines and for our understanding of different profiles of susceptibility to these major pathogens. IMPORTANCE Influenza virus causes half a million deaths annually. CD4؉ T cell responses have been shown to be important for protection against influenza and for recovery. CD4؉ T cell responses are also critical for efficient CD8 ؉ T cell response and antibody response. As immunodominant T cells generally play a more important role, characterizing these immunodominant responses is critical for influenza vaccine development. We show here that the internal matrix protein 1 (M1) and nucleoprotein (NP), rather than the surface proteins reported previously, are the immunodominant targets of CD4 ؉ T cell responses. Interestingly, these immunodominant epitope regions accumulated many mutations over time, which likely indicates increased immune pressure. These findings have significant implications for the design of T cell-based influenza vaccines.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Immunodominant CD4⁺T-Cell Responses to Influenza A Virus in Healthy Individuals Focus on Matrix 1 and Nucleoprotein

Chen

Zanker

Xiao

et al. 2014

J Virol

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“…The epitopes are identified as amino acids 73-385 and 438-452 on UreB, amino acids 83-97 and 58-72 on Lpp20, and amino acids 88-100 on HpaA. [122][123][124] Among these identified epitopes, the MHCII molecule HLA-DRB1*1501 restricted immunodominant CD4+ T-cell response to HpaA 88-100 is associated with reduced risk of severe gastric diseases. 123 These findings indicate that efficient antigen presentation and recognition of certain H. pylori antigens by TCRs could influence the outcome of associated pathologies.…”

Section: Receptor-dependent Activities Of Vaca On Dcs and Macrophagesmentioning

confidence: 99%

“…[122][123][124] Among these identified epitopes, the MHCII molecule HLA-DRB1*1501 restricted immunodominant CD4+ T-cell response to HpaA 88-100 is associated with reduced risk of severe gastric diseases. 123 These findings indicate that efficient antigen presentation and recognition of certain H. pylori antigens by TCRs could influence the outcome of associated pathologies. Therefore, further studies on antigen processing, presentation, and recognition during H. pylori infection are required to understand the deregulation of immune responses against this pathogen.…”

Section: Receptor-dependent Activities Of Vaca On Dcs and Macrophagesmentioning

confidence: 99%

Signal transduction of Helicobacter pylori during interaction with host cell protein receptors of epithelial and immune cells

Pachathundikandi

Tegtmeyer²,

Backert³

2013

Gut Microbes

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“…However, little is known about the human CD4 + T cell responses to HpaA in H. pylori infected individuals. Using a systematic approach, we have identified and characterized several immunodominant CD4 + T cell responses specific to HpaA in our previous study [20]. The immunodominant CD4 + T cell responses specific to HpaA88-100 were observed in most H. pylori infected individuals who expressed HLA-DRB1*1501 and were significantly more abundant in patients with less severe gastric diseases [20].…”

Section: Introductionmentioning

confidence: 99%

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

Chen

Yang

et al. 2016

Oncotarget

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In mice, antigen-specific CD4+ T cell response is indispensible for the protective immunity against Helicobacter pylori (H. pylori). It has been demonstrated that neuraminyllactose-binding hemagglutinin (HpaA) immunization protected mice from H. pylori infection in a CD4+ T cell dependent manner. However, much remains unclear concerning the human CD4+ T cell responses to HpaA. We conducted a systematic study here to explore the immunodominant, HpaA-specific CD4+ T cell responses in H. pylori infected individuals. We found that HpaA-specific CD4+ T cell responses varied remarkably in their magnitude and had broad epitope-specificity. Importantly, the main responses focused on two regions: HpaA76-105 and HpaA130-159. The HLA-DRB1*0901 restricted HpaA142-159 specific CD4+ T cell response was the most immunodominant response at a population level. The immunodominant epitope HpaA142-159 was naturally presented and highly conserved. We also demonstrated that it was not the broad peptide specificity, but the strength of HpaA specific CD4+ T cell responses associated with gastric diseases potentially caused by H. pylori infection. Such investigation will aid development of novel vaccines against H. pylori infection.

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A Dominant CD4+ T-Cell Response to Helicobacter pylori Reduces Risk for Gastric Disease in Humans

Cited by 35 publications

References 35 publications

Immunodominant CD4⁺T-Cell Responses to Influenza A Virus in Healthy Individuals Focus on Matrix 1 and Nucleoprotein

Immunodominant CD4⁺T-Cell Responses to Influenza A Virus in Healthy Individuals Focus on Matrix 1 and Nucleoprotein

Signal transduction of Helicobacter pylori during interaction with host cell protein receptors of epithelial and immune cells

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

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A Dominant CD4+ T-Cell Response to Helicobacter pylori Reduces Risk for Gastric Disease in Humans

Cited by 35 publications

References 35 publications

Immunodominant CD4+T-Cell Responses to Influenza A Virus in Healthy Individuals Focus on Matrix 1 and Nucleoprotein

Immunodominant CD4+T-Cell Responses to Influenza A Virus in Healthy Individuals Focus on Matrix 1 and Nucleoprotein

Signal transduction of Helicobacter pylori during interaction with host cell protein receptors of epithelial and immune cells

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

Contact Info

Product

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Immunodominant CD4⁺T-Cell Responses to Influenza A Virus in Healthy Individuals Focus on Matrix 1 and Nucleoprotein

Immunodominant CD4⁺T-Cell Responses to Influenza A Virus in Healthy Individuals Focus on Matrix 1 and Nucleoprotein