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A novel strategy to screen Bacillus Calmette-Guerin protein antigen recognized by ?? TCR.

ABSTRACT:

Background

Phosphoantigen was originally identified as the main ?? TCR-recognized antigen that could activate ?? T cells to promote immune protection against mycobacterial infection. However, new evidence shows that the ?? T cells activated by phosphoantigen can only provide partial immune protection against mycobacterial infection. In contrast, whole lysates of Mycobacterium could activate immune protection more potently, implying that other ?? TCR-recognized antigens that elicit protective immune responses. To date, only a few distinct mycobacterial antigens recognized by the ?? TCR have been characterized.

Methodology/principal findings

In the present study, we established a new approach to screen epitopes or protein antigens recognized by the ?? TCR using Bacillus Calmette-Guérin- (BCG-) specific ? TCR transfected cells as probes to pan a 12-mer random-peptide phage-displayed library. Through binding assays and functional analysis, we identified a peptide (BP3) that not only binds to the BCG-specific ?? TCR but also effectively activates ?? T cells isolated from human subjects inoculated with BCG. Importantly, the ?? T cells activated by peptide BP3 had a cytotoxic effect on THP-1 cells infected with BCG. Moreover, the oxidative stress response regulatory protein (OXYS), a BCG protein that matches perfectly with peptide BP3 according to bioinformatics analysis, was confirmed as a ligand for the ?? TCR and was found to activate ?? T cells from human subjects inoculated with BCG.

Conclusions/significance

In conclusion, our study provides a novel strategy to identify epitopes or protein antigens for the ?? TCR, and provides a potential means to screen mycobacterial vaccines or candidates for adjuvant.

SUBMITTER: Xi X

PROVIDER: S-EPMC3081299 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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A novel strategy to screen Bacillus Calmette-Guérin protein antigen recognized by γδ TCR.

Xi XueYan X Zhang XiaoYan X Wang Bei B Wang Ji J Huang He H Cui LianXian L Han XiQin X Li Liang L He Wei W Zhao ZhenDong Z

PloS one 20110422 4

<h4>Background</h4>Phosphoantigen was originally identified as the main γδ TCR-recognized antigen that could activate γδ T cells to promote immune protection against mycobacterial infection. However, new evidence shows that the γδ T cells activated by phosphoantigen can only provide partial immune protection against mycobacterial infection. In contrast, whole lysates of Mycobacterium could activate immune protection more potently, implying that other γδ TCR-recognized antigens that elicit protec ...[more]

PMID: 21526117

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Project description:BackgroundThe Bacillus Calmette-Guerin (BCG) vaccine has been in use for 99 years, and is regarded as one of the oldest human vaccines known today. It is recommended primarily due to its effect in preventing the most severe forms of tuberculosis, including disseminated tuberculosis and meningeal tuberculosis in children; however, its efficacy in preventing pulmonary tuberculosis and TB reactivation in adults has been questioned. Several studies however have found that asides from its role in tuberculosis prevention, the BCG vaccine also has protective effects against a host of other viral infections in humans, an effect which has been termed: heterologous, non-specific or off-target.ObjectivesAs we approach 100 years since the discovery of the BCG vaccine, we review the evidence of the non-specific protection offered by the vaccine against viral infections, discuss the possible mechanisms of action of these effects, highlight the implications these effects could have on vaccinology and summarize the recent epidemiological correlation between the vaccine and the on-going COVID-19 pandemic.ResultsSeveral epidemiological studies have established that BCG does reduce all-cause mortality in infants, and also the time of vaccination influences this effect significantly. This effect has been attributed to the protective effect of the vaccine in preventing unrelated viral infections during the neonatal period. Some of such viral infections that have been investigated include: herpes simplex virus (HSV), human Papilloma virus (HPV), yellow fever virus (YFV), respiratory syncytial virus (RSV) and influenza virus type A (H1N1). These effects are thought to be mediated via induction of innate immune memory as well as heterologous lymphocytic activation. While epidemiological studies have suggested a correlation, the potential protection of the BCG vaccine against COVID-19 transmission and mortality rates is currently unclear. Ongoing clinical trials and further research may shed more light on the subject in the future.ConclusionBCG is a multifaceted vaccine, with many numerous potential applications to vaccination strategies being employed for current and future viral infections. There however is a need for further studies into the immunologic mechanisms behind these non-specific effects, for these potentials to become reality, as we usher in the beginning of the second century since the vaccine's discovery.