Xiao, ZYe, ZTadwal, V.SShen, MRen, E.CMICROBIOLOGY AND IMMUNOLOGY2020-10-202020-10-202017Xiao, Z, Ye, Z, Tadwal, V.S, Shen, M, Ren, E.C (2017). Dual non-contiguous peptide occupancy of HLA class i evoke antiviral human CD8 T cell response and form neo-epitopes with self-antigens /631/250/21/324/1509 /631/326/596/1553 /13/31 /13/106 /13/109 /145 /82/83 article. Scientific Reports 7 (1) : 5072. ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-017-05171-w20452322https://scholarbank.nus.edu.sg/handle/10635/178315Host 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. © 2017 The Author(s).Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/antivirus agentautoantigenepitopeHLA antigen class 1lymphocyte antigen receptorpeptidealleleamino acid sequencebinding siteCD8+ T lymphocytechemistryhumanimmunologylymphocyte activationmetabolismprotein stabilitystatic electricityAllelesAmino Acid SequenceAntiviral AgentsAutoantigensBinding SitesCD8-Positive T-LymphocytesEpitopesHistocompatibility Antigens Class IHumansLymphocyte ActivationPeptidesProtein StabilityReceptors, Antigen, T-Cell, alpha-betaStatic ElectricityArticle