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Nat Commun. 2018 Jul 13;9(1):2716. doi: 10.1038/s41467-018-05288-0.

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

Author information

1
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore, 117545, Singapore.
2
Immunology Programme, Life Sciences Institute, National University of Singapore, 28 Medical Drive, Centre for Life Sciences, Level 3, Singapore, 117456, Singapore.
3
Emerging Infectious Diseases Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore, 169857, Singapore.
4
Division of Infection and Immunity, Cardiff University School of Medicine, Henry Wellcome Building, University Hospital Wales, Heath Park, Cardiff, CF14 4XN, United Kingdom.
5
Singapore Immunology Network, A*STAR, 8A Biomedical Grove, Immunos #03-06, Singapore, 138648, Singapore.
6
Systems Immunity Research Institute, Cardiff University, Tenovus Building, Cardiff, CF14 4XN, United Kingdom.
7
NUS Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore, Centre for Life Sciences (CeLS), #05-01, 28 Medical Drive, Singapore, 117456, Singapore.
8
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore, 117545, Singapore. micjmb@nus.edu.sg.
9
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore, 117545, Singapore. micnrjg@nus.edu.sg.
10
Immunology Programme, Life Sciences Institute, National University of Singapore, 28 Medical Drive, Centre for Life Sciences, Level 3, Singapore, 117456, Singapore. micnrjg@nus.edu.sg.
11
NUS Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore, Centre for Life Sciences (CeLS), #05-01, 28 Medical Drive, Singapore, 117456, Singapore. micnrjg@nus.edu.sg.

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.

PMID:
30006605
PMCID:
PMC6045629
DOI:
10.1038/s41467-018-05288-0
[Indexed for MEDLINE]
Free PMC Article

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