A Novel Strategy to Screen Bacillus Calmette-Guérin Protein Antigen Recognized by γδ TCRReport as inadecuate




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Background

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 protective immune responses. To date, only a few distinct mycobacterial antigens recognized by the γδ 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 γδ TCR using Bacillus Calmette-Guérin- BCG- specific γ 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 γδ TCR but also effectively activates γδ T cells isolated from human subjects inoculated with BCG. Importantly, the γδ 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 γδ TCR and was found to activate γδ 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 γδ TCR, and provides a potential means to screen mycobacterial vaccines or candidates for adjuvant.



Author: XueYan Xi, XiaoYan Zhang, Bei Wang, Ji Wang, He Huang, LianXian Cui, XiQin Han, Liang Li, Wei He , ZhenDong Zhao

Source: http://plos.srce.hr/



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