文章基本信息

标题：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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作者：Ziwei Xiao ; Zhiyong Ye ; Vikeramjeet Singh Tadwal 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2017
卷号：7
期号：1
DOI：10.1038/s41598-017-05171-w
语种：English
出版社：Springer Nature
摘要：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.