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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.


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 ?2-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.

SUBMITTER: Xiao Z 

PROVIDER: S-EPMC5505988 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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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.

Xiao Ziwei Z   Ye Zhiyong Z   Tadwal Vikeramjeet Singh VS   Shen Meixin M   Ren Ee Chee EC  

Scientific reports 20170711 1


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<sup>+</sup> cells. Surprisingly, two peptide fragments between 4-7-mer derived from LMP2<sub>(340-349)</sub> were  ...[more]

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