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- Title
Nonstimulatory peptide–MHC enhances human T-cell antigen-specific responses by amplifying proximal TCR signaling.
- Authors
Xiang Zhao; Sankaran, Shvetha; Jiawei Yap; Chien Tei Too; Zi Zong Ho; Dolton, Garry; Legut, Mateusz; Ee Chee Ren; Sewell, Andrew K.; Bertoletti, Antonio; MacAry, Paul A.; Brzostek, Joanna; Gascoigne, Nicholas R. J.
- 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.
- Publication
Nature Communications, 2018, Vol 9, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-018-05288-0