Nonstimulatory peptide-MHC enhances human T-cell antigen-specific responses by amplifying proximal TCR signaling

Nature Communications
Xiang ZhaoNicholas R J Gascoigne

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.

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Citations

Jan 15, 2020·Nature Immunology·Joanna BrzostekNicholas R J Gascoigne
May 27, 2020·Cellular & Molecular Immunology·Ling WuNicholas R J Gascoigne
Aug 14, 2019·Immunological Reviews·Audrey Connolly, Etienne Gagnon
Oct 29, 2021·Frontiers in Immunology·Xiang ZhaoJoanna Brzostek

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Methods Mentioned

BETA
flow cytometry
ELISA
fluorescence microscopy

Software Mentioned

GraphPad Prism

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