Dual non-contiguous peptide occupancy of HLA class I evoke antiviral human CD8 T cell response and form neo-epitopes with self-antigens

Abstract Host CD8 T cell response to viral infections involves recognition of 8–10-mer peptides presented by MHC-I molecules. However, proteasomes generate predominantly 2–7-mer peptides, but the role of these peptides is largely unknown. Here, we show that single short peptides of <8-mer from La...

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Autores principales:	Ziwei Xiao, Zhiyong Ye, Vikeramjeet Singh Tadwal, Meixin Shen, Ee Chee Ren
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fe12bf6e4a344a39932782c4d4bcc2ed
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spelling	oai:doaj.org-article:fe12bf6e4a344a39932782c4d4bcc2ed2021-12-02T15:05:02ZDual non-contiguous peptide occupancy of HLA class I evoke antiviral human CD8 T cell response and form neo-epitopes with self-antigens10.1038/s41598-017-05171-w2045-2322https://doaj.org/article/fe12bf6e4a344a39932782c4d4bcc2ed2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05171-whttps://doaj.org/toc/2045-2322Abstract Host CD8 T cell response to viral infections involves recognition of 8–10-mer peptides presented by MHC-I molecules. However, proteasomes generate predominantly 2–7-mer peptides, but the role of these peptides is largely unknown. Here, we show that single short peptides of <8-mer from Latent Membrane Protein 2 (LMP2) of Epstein Barr Virus (EBV) can bind HLA-A*11:01 and stimulate CD8+ cells. Surprisingly, two peptide fragments between 4–7-mer derived from LMP2(340–349) were able to complement each other, forming combination epitopes that can stimulate specific CD8+ T cell responses. Moreover, peptides from self-antigens can complement non-self peptides within the HLA binding cleft, forming neoepitopes. Solved structures of a tetra-complex comprising two peptides, HLA and β2-microglobulin revealed the free terminals of the two peptides to adopt an upward conformation directed towards the T cell receptor. Our results demonstrate a previously unknown mix-and-match combination of dual peptide occupancy in HLA that can generate vast combinatorial complexity.Ziwei XiaoZhiyong YeVikeramjeet Singh TadwalMeixin ShenEe Chee RenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ziwei Xiao Zhiyong Ye Vikeramjeet Singh Tadwal Meixin Shen Ee Chee Ren Dual non-contiguous peptide occupancy of HLA class I evoke antiviral human CD8 T cell response and form neo-epitopes with self-antigens
description	Abstract Host CD8 T cell response to viral infections involves recognition of 8–10-mer peptides presented by MHC-I molecules. However, proteasomes generate predominantly 2–7-mer peptides, but the role of these peptides is largely unknown. Here, we show that single short peptides of <8-mer from Latent Membrane Protein 2 (LMP2) of Epstein Barr Virus (EBV) can bind HLA-A*11:01 and stimulate CD8+ cells. Surprisingly, two peptide fragments between 4–7-mer derived from LMP2(340–349) were able to complement each other, forming combination epitopes that can stimulate specific CD8+ T cell responses. Moreover, peptides from self-antigens can complement non-self peptides within the HLA binding cleft, forming neoepitopes. Solved structures of a tetra-complex comprising two peptides, HLA and β2-microglobulin revealed the free terminals of the two peptides to adopt an upward conformation directed towards the T cell receptor. Our results demonstrate a previously unknown mix-and-match combination of dual peptide occupancy in HLA that can generate vast combinatorial complexity.
format	article
author	Ziwei Xiao Zhiyong Ye Vikeramjeet Singh Tadwal Meixin Shen Ee Chee Ren
author_facet	Ziwei Xiao Zhiyong Ye Vikeramjeet Singh Tadwal Meixin Shen Ee Chee Ren
author_sort	Ziwei Xiao
title	Dual non-contiguous peptide occupancy of HLA class I evoke antiviral human CD8 T cell response and form neo-epitopes with self-antigens
title_short	Dual non-contiguous peptide occupancy of HLA class I evoke antiviral human CD8 T cell response and form neo-epitopes with self-antigens
title_full	Dual non-contiguous peptide occupancy of HLA class I evoke antiviral human CD8 T cell response and form neo-epitopes with self-antigens
title_fullStr	Dual non-contiguous peptide occupancy of HLA class I evoke antiviral human CD8 T cell response and form neo-epitopes with self-antigens
title_full_unstemmed	Dual non-contiguous peptide occupancy of HLA class I evoke antiviral human CD8 T cell response and form neo-epitopes with self-antigens
title_sort	dual non-contiguous peptide occupancy of hla class i evoke antiviral human cd8 t cell response and form neo-epitopes with self-antigens
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/fe12bf6e4a344a39932782c4d4bcc2ed
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Dual non-contiguous peptide occupancy of HLA class I evoke antiviral human CD8 T cell response and form neo-epitopes with self-antigens

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