PDBsum entry 5grd

Immune system

PDB id: 5grd

Contents

Protein chains

274 a.a.

99 a.a.

Ligands

SER-SER-CYS-SER-SER-CYS-PRO-LEU-SER-LYS

GOL ×2

Waters ×413

PDB id:

5grd

Name:

Immune system

Title:

Crystal structure of 10-mer peptide from ebv in complex with hla- a1101.

Structure:

Hla class i histocompatibility antigen, a-11 alpha chain. Chain: a. Fragment: unp residues 25-299. Synonym: mhc class i antigen a 11. Engineered: yes. Other_details: fragment: extracellular domain alpha 1, alpha 2 and alpha 3.. Beta-2-microglobulin. Chain: b.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-a, hlaa. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: b2m, cdabp0092, hdcma22p. Synthetic: yes. Synthetic construct.

Resolution:

1.80Å R-factor: 0.179 R-free: 0.226

Authors:

V.S.Tadwal,Z.Xiao,E.C.Ren

Key ref:

Z.Xiao et al. (2017). 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. PubMed id: 28698575

Date:

10-Aug-16 Release date: 09-Aug-17

Protein chain

P04439  (1A03_HUMAN) -  HLA class I histocompatibility antigen, A alpha chain from Homo sapiens

Seq: 365 a.a.

Struc: 274 a.a.*

Protein chain

P61769  (B2MG_HUMAN) -  Beta-2-microglobulin from Homo sapiens

Seq: 119 a.a.

Struc: 99 a.a.

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

Sci Rep 7:5072 (2017)

PubMed id: 28698575

Dual non-contiguous peptide occupancy of HLA class I evoke antiviral human CD8 T cell response and form neo-epitopes with self-antigens.

Z.Xiao, Z.Ye, V.S.Tadwal, M.Shen, E.C.Ren.

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 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.