5GRG

Crystal structure of dual peptide from EBV in complex with HLA-A*11:01

Summary for 5GRG

• Entry DOI: 10.2210/pdb5grg/pdb
• Related: 5GRD
• Descriptor: HLA class I histocompatibility antigen, A-11 alpha chain, Beta-2-microglobulin, Epstein Barr Virus, Latent Membrane Protein 2 epitope, ... (6 entities in total)
• Functional Keywords: immune system, human leukocyte antigen
• Biological source: Homo sapiens (Human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P13746; Secreted . Note=(Microbial infection) In the presence of M: P61769
• Total number of polymer chains: 4
• Total formula weight: 44988.74

Authors

Tadwal, V.S.,Xiao, Z.,Ren, E.C. (deposition date: 2016-08-11, release date: 2017-08-09, Last modification date: 2023-11-08)

Primary citation

Xiao, Z.,Ye, Z.,Tadwal, V.S.,Shen, M.,Ren, E.C.
Dual non-contiguous peptide occupancy of HLA class I evoke antiviral human CD8 T cell response and form neo-epitopes with self-antigens
Sci Rep, 7:5072-5072, 2017

PubMed 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 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.

PubMed: 28698575
DOI: 10.1038/s41598-017-05171-w

Experimental method

X-RAY DIFFRACTION (1.94 Å)