Molecular Basis of a Dominant SARS-CoV-2 Spike-Derived Epitope Presented by HLA-A*02:01 Recognised by a Public TCR.

Autor:	Szeto C; Viral and Structural Immunology Laboratory, Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, School of Molecular Sciences, La Trobe University, Bundoora, VIC 3086, Australia.; Viral and Structural Immunology Laboratory, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia., Nguyen AT; Viral and Structural Immunology Laboratory, Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, School of Molecular Sciences, La Trobe University, Bundoora, VIC 3086, Australia.; Viral and Structural Immunology Laboratory, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia., Lobos CA; Viral and Structural Immunology Laboratory, Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, School of Molecular Sciences, La Trobe University, Bundoora, VIC 3086, Australia.; Viral and Structural Immunology Laboratory, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia., Chatzileontiadou DSM; Viral and Structural Immunology Laboratory, Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, School of Molecular Sciences, La Trobe University, Bundoora, VIC 3086, Australia.; Viral and Structural Immunology Laboratory, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia., Jayasinghe D; Viral and Structural Immunology Laboratory, Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, School of Molecular Sciences, La Trobe University, Bundoora, VIC 3086, Australia.; Viral and Structural Immunology Laboratory, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia., Grant EJ; Viral and Structural Immunology Laboratory, Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, School of Molecular Sciences, La Trobe University, Bundoora, VIC 3086, Australia.; Viral and Structural Immunology Laboratory, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia., Riboldi-Tunnicliffe A; Australian Synchrotron, ANSTO, Clayton, VIC 3168, Australia., Smith C; QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.; Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia., Gras S; Viral and Structural Immunology Laboratory, Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, School of Molecular Sciences, La Trobe University, Bundoora, VIC 3086, Australia.; Viral and Structural Immunology Laboratory, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
Jazyk:	angličtina
Zdroj:	Cells [Cells] 2021 Oct 03; Vol. 10 (10). Date of Electronic Publication: 2021 Oct 03.
DOI:	10.3390/cells10102646
Abstrakt:	The data currently available on how the immune system recognises the SARS-CoV-2 virus is growing rapidly. While there are structures of some SARS-CoV-2 proteins in complex with antibodies, which helps us understand how the immune system is able to recognise this new virus; however, we lack data on how T cells are able to recognise this virus. T cells, especially the cytotoxic CD8+ T cells, are critical for viral recognition and clearance. Here we report the X-ray crystallography structure of a T cell receptor, shared among unrelated individuals (public TCR) in complex with a dominant spike-derived CD8+ T cell epitope (YLQ peptide). We show that YLQ activates a polyfunctional CD8+ T cell response in COVID-19 recovered patients. We detail the molecular basis for the shared TCR gene usage observed in HLA-A*02:01+ individuals, providing an understanding of TCR recognition towards a SARS-CoV-2 epitope. Interestingly, the YLQ peptide conformation did not change upon TCR binding, facilitating the high-affinity interaction observed.
Databáze:	MEDLINE
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