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
Xiao, Z Ye, Z Tadwal, V.S Shen, M Ren, E.C
Xiao, Z
Ye, Z
Tadwal, V.S
Shen, M
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Alternative Title
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. © 2017 The Author(s).
Keywords
antivirus agent, autoantigen, epitope, HLA antigen class 1, lymphocyte antigen receptor, peptide, allele, amino acid sequence, binding site, CD8+ T lymphocyte, chemistry, human, immunology, lymphocyte activation, metabolism, protein stability, static electricity, Alleles, Amino Acid Sequence, Antiviral Agents, Autoantigens, Binding Sites, CD8-Positive T-Lymphocytes, Epitopes, Histocompatibility Antigens Class I, Humans, Lymphocyte Activation, Peptides, Protein Stability, Receptors, Antigen, T-Cell, alpha-beta, Static Electricity
Source Title
Scientific Reports
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Series/Report No.
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Rights
Attribution 4.0 International
Date
2017
DOI
10.1038/s41598-017-05171-w
Type
Article