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Crystal structure of suboptimal viral fragments of Epstein Barr Virus Rta peptide-HLA complex that stimulate CD8 T cell response.

ABSTRACT: Peptides presented by Human leukocyte antigen (HLA) class-I molecules are generally 8-10 amino acids in length. However, the predominant pool of peptide fragments generated by proteasomes is less than 8 amino acids in length. Using the Epstein - Barr virus (EBV) Rta-epitope (ATIGTAMYK, residues 134-142) restricted by HLA-A*11:01 which generates a strong immunodominant response, we investigated the minimum length of a viral peptide that can constitute a viral epitope recognition by CD8 T cells. The results showed that Peripheral blood mononuclear cells (PBMCs) from healthy donors can be stimulated by a viral peptide fragment as short as 4-mer (AMYK), together with a 5-mer (ATIGT) to recapitulate the full length EBV Rta epitope. This was confirmed by generating crystals of the tetra-complex (2 peptides, HLA and ?2-microglobulin). The solved crystal structure of HLA-A*11:01 in complex with these two short peptides revealed that they can bind in the same orientation similar to parental peptide (9-mer) and the free ends of two short peptides acquires a bulged conformation that is directed towards the T cell receptor. Our data shows that suboptimal length of 4-mer and 5-mer peptides can complement each other to form a stable peptide-MHC (pMHC) complex.

SUBMITTER: Huan X

PROVIDER: S-EPMC6853878 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Crystal structure of suboptimal viral fragments of Epstein Barr Virus Rta peptide-HLA complex that stimulate CD8 T cell response.

Huan Xuelu X Zhuo Ziyi Z Xiao Ziwei Z Ren Ee Chee EC

Scientific reports 20191113 1

Peptides presented by Human leukocyte antigen (HLA) class-I molecules are generally 8-10 amino acids in length. However, the predominant pool of peptide fragments generated by proteasomes is less than 8 amino acids in length. Using the Epstein - Barr virus (EBV) Rta-epitope (ATIGTAMYK, residues 134-142) restricted by HLA-A*11:01 which generates a strong immunodominant response, we investigated the minimum length of a viral peptide that can constitute a viral epitope recognition by CD8 T cells. T ...[more]

PMID: 31723204

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Dataset Information

Crystal structure of suboptimal viral fragments of Epstein Barr Virus Rta peptide-HLA complex that stimulate CD8 T cell response.

Publications

Crystal structure of suboptimal viral fragments of Epstein Barr Virus Rta peptide-HLA complex that stimulate CD8 T cell response.

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