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PDBsum entry 5grd
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Immune system
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PDB id
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5grd
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References listed in PDB file
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Key reference
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Title
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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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Authors
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Z.Xiao,
Z.Ye,
V.S.Tadwal,
M.Shen,
E.C.Ren.
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Ref.
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Sci Rep, 2017,
7,
5072.
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PubMed id
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Abstract
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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.
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