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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
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 Memb...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5505988/ https://www.ncbi.nlm.nih.gov/pubmed/28698575 http://dx.doi.org/10.1038/s41598-017-05171-w |
Sumario: | 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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