PDBsum entry 2zsv

Immune system

PDB id: 2zsv

Contents

Protein chains

274 a.a. *

99 a.a. *

Ligands

ARG-ABA-GLN-ILE-PHE-ALA-ASN-ILE ×2

GOL ×10

CYS

Waters ×616

* Residue conservation analysis

PDB id:

2zsv

Name:

Immune system

Title:

Crystal structure of h-2kb in complex with jhmv epitope s598

Structure:

H-2 class i histocompatibility antigen, k-b alpha chain. Chain: a, c. Fragment: extracellular domain. Synonym: h-2k(b). Engineered: yes. Beta-2-microglobulin. Chain: b, d. Engineered: yes. 8-mer peptide from spike glycoprotein.

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: h2-k1, h2-k. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: b2m. Synthetic: yes. Other_details: the peptide was chemically synthesized. The sequence

Resolution:

1.80Å R-factor: 0.212 R-free: 0.250

Authors:

A.Theodossis,M.A.Dunstone,J.Rossjohn

Key ref:

N.S.Butler et al. (2008). Prevention of cytotoxic T cell escape using a heteroclitic subdominant viral T cell determinant. Plos Pathog, 4, e1000186. PubMed id: 18949029

Date:

18-Sep-08 Release date: 04-Nov-08

Protein chains

P01901  (HA1B_MOUSE) -  H-2 class I histocompatibility antigen, K-B alpha chain from Mus musculus

Seq: 369 a.a.

Struc: 274 a.a.

Protein chains

P01887  (B2MG_MOUSE) -  Beta-2-microglobulin from Mus musculus

Seq: 119 a.a.

Struc: 99 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: Chains A, B, C, D: E.C.?

Plos Pathog 4:e1000186 (2008)

PubMed id: 18949029

Prevention of cytotoxic T cell escape using a heteroclitic subdominant viral T cell determinant.

N.S.Butler, A.Theodossis, A.I.Webb, R.Nastovska, S.H.Ramarathinam, M.A.Dunstone, J.Rossjohn, A.W.Purcell, S.Perlman.

ABSTRACT

High affinity antigen-specific T cells play a critical role during protective immune responses. Epitope enhancement can elicit more potent T cell responses and can subsequently lead to a stronger memory pool; however, the molecular basis of such enhancement is unclear. We used the consensus peptide-binding motif for the Major Histocompatibility Complex molecule H-2K(b) to design a heteroclitic version of the mouse hepatitis virus-specific subdominant S598 determinant. We demonstrate that a single amino acid substitution at a secondary anchor residue (Q to Y at position 3) increased the stability of the engineered determinant in complex with H-2K(b). The structural basis for this enhanced stability was associated with local alterations in the pMHC conformation as a result of the Q to Y substitution. Recombinant viruses encoding this engineered determinant primed CTL responses that also reacted to the wildtype epitope with significantly higher functional avidity, and protected against selection of virus mutated at a second CTL determinant and consequent disease progression in persistently infected mice. Collectively, our findings provide a basis for the enhanced immunogenicity of an engineered determinant that will serve as a template for guiding the development of heteroclitic T cell determinants with applications in prevention of CTL escape in chronic viral infections as well as in tumor immunity.