PDBsum entry 3mgo

Immune system

PDB id: 3mgo

Contents

Protein chains

275 a.a. *

100 a.a. *

Ligands

ARG-LEU-TYR-GLN-ASN-PRO-THR-THR-TYR-ILE ×4

Waters ×974

* Residue conservation analysis

PDB id:

3mgo

Name:

Immune system

Title:

Crystal structure of a h5-specific ctl epitope derived from h5n1 influenza virus in complex with hla-a 0201

Structure:

Hla class i histocompatibility antigen, a-2 alpha chain. Chain: a, d, g, j. Fragment: extracellular domain, unp residues 25-275. Synonym: hla-a 0201 Heavy chain, mhc class i antigen a 2. Engineered: yes. Beta-2-microglobulin. Chain: b, e, h, k. Synonym: beta-2-microglobulin form pi 5.3. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-a 0201 Heavy chain. Expressed in: escherichia coli. Expression_system_taxid: 469008. Gene: beta2 microglobin. Synthetic: yes. Influenza a virus.

Resolution:

2.30Å R-factor: 0.205 R-free: 0.247

Authors:

Y.Sun,J.Liu,M.Yang,F.Gao,J.Zhou,Y.Kitamura

Key ref:

Y.Sun et al. (2010). Identification and structural definition of H5-specific CTL epitopes restricted by HLA-A*0201 derived from the H5N1 subtype of influenza A viruses. J Gen Virol, 91, 919-930. PubMed id: 19955560

Date:

07-Apr-10 Release date: 19-May-10

Protein chains

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

Seq: 365 a.a.

Struc: 275 a.a.*

Protein chains

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

Seq: 119 a.a.

Struc: 100 a.a.*

* PDB and UniProt seqs differ at 20 residue positions (black crosses)

J Gen Virol 91:919-930 (2010)

PubMed id: 19955560

Identification and structural definition of H5-specific CTL epitopes restricted by HLA-A*0201 derived from the H5N1 subtype of influenza A viruses.

Y.Sun, J.Liu, M.Yang, F.Gao, J.Zhou, Y.Kitamura, B.Gao, P.Tien, Y.Shu, A.Iwamoto, Z.Chen, G.F.Gao.

ABSTRACT

The haemagglutinin (HA) glycoprotein of influenza A virus is a major antigen that initiates humoral immunity against infection; however, the cellular immune response against HA is poorly understood. Furthermore, HA-derived cytotoxic T-lymphocyte (CTL) epitopes are relatively rare in comparison to other internal gene products. Here, CTL epitopes of the HA serotype H5 protein were screened. By using in silico prediction, in vitro refolding and a T2 cell-binding assay, followed by immunization of HLA-A2.1/K(b) transgenic mice, an HLA-A*0201-restricted decameric epitope, RI-10 (H5 HA205-214, RLYQNPTTYI), was shown to elicit a robust CTL epitope-specific response. In addition, RI-10 and its variant, KI-10 (KLYQNPTTYI), were also demonstrated to be able to induce a higher CTL epitope-specific response than the influenza A virus dominant CTL epitope GL-9 (GILGFVFTL) in peripheral blood mononuclear cells of HLA-A*0201-positive patients who had recovered from H5N1 virus infection. Furthermore, the crystal structures of RI-10-HLA-A*0201 and KI-10-HLA-A*0201 complexes were determined at 2.3 and 2.2 A resolution, respectively, showing typical HLA-A*0201-restricted epitopes. The conformations of RI-10 and KI-10 in the antigen-presenting grooves in crystal structures of the two complexes show significant differences, despite their nearly identical sequences. These results provide implications for the discovery of diagnostic markers and the design of novel influenza vaccines.