Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-018-05288-0
Title: Nonstimulatory peptide-MHC enhances human T-cell antigen-specific responses by amplifying proximal TCR signaling
Authors: Zhao X. 
Sankaran S. 
Yap J. 
Too C.T. 
Ho Z.Z. 
Dolton G.
Legut M.
Ren E.C. 
Sewell A.K.
Bertoletti A. 
MacAry P.A. 
Brzostek J. 
Gascoigne N.R.J. 
Issue Date: 2018
Publisher: Nature Publishing Group
Citation: Zhao X., Sankaran S., Yap J., Too C.T., Ho Z.Z., Dolton G., Legut M., Ren E.C., Sewell A.K., Bertoletti A., MacAry P.A., Brzostek J., Gascoigne N.R.J. (2018). Nonstimulatory peptide-MHC enhances human T-cell antigen-specific responses by amplifying proximal TCR signaling. Nature Communications 9 (1) : 2716. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-018-05288-0
Abstract: Foreign antigens are presented by antigen-presenting cells in the presence of abundant endogenous peptides that are nonstimulatory to the T cell. In mouse T cells, endogenous, nonstimulatory peptides have been shown to enhance responses to specific peptide antigens, a phenomenon termed coagonism. However, whether coagonism also occurs in human T cells is unclear, and the molecular mechanism of coagonism is still under debate since CD4 and CD8 coagonism requires different interactions. Here we show that the nonstimulatory, HIV-derived peptide GAG enhances a specific human cytotoxic T lymphocyte response to HBV-derived epitopes presented by HLA-A 02:01. Coagonism in human T cells requires the CD8 coreceptor, but not T-cell receptor (TCR) binding to the nonstimulatory peptide-MHC. Coagonists enhance the phosphorylation and recruitment of several molecules involved in the TCR-proximal signaling pathway, suggesting that coagonists promote T-cell responses to antigenic pMHC by amplifying TCR-proximal signaling. © 2018 The Author(s).
Source Title: Nature Communications
URI: http://scholarbank.nus.edu.sg/handle/10635/152565
ISSN: 20411723
DOI: 10.1038/s41467-018-05288-0
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