PDBsum entry 2qrt

Immune system

PDB id: 2qrt

Contents

Protein chains

398 a.a. *

Waters ×755

* Residue conservation analysis

PDB id:

2qrt

Name:

Immune system

Title:

Crystal structure of a disulfide trapped single chain trimer composed of the mhc i heavy chain h-2kb y84c, beta-2microglobulin, and ovalbumin-derived peptide.

Structure:

H-2 class i histocompatibility antigen k-b alpha chain, beta-2 microglobulin, ovalbumin-derived peptide. Chain: a, b. Fragment: fusion protein of ovalbumin-derived peptide, linker, beta-2 microglobulin, linker, and h-2 class i histocompatibility antigen k-b alpha chain extracellular domain. Synonym: h-2kb. Engineered: yes. Mutation: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: h2-k1, h2-k, b2m. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.80Å R-factor: 0.208 R-free: 0.239

Authors:

V.E.Mitaksov,D.H.Fremont

Key ref:

V.Mitaksov et al. (2007). Structural engineering of pMHC reagents for T cell vaccines and diagnostics. Chem Biol, 14, 909-922. PubMed id: 17719490

Date:

29-Jul-07 Release date: 06-Nov-07

Protein chains

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

Seq: 119 a.a.

Struc: 398 a.a.*

Protein chains

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

Seq: 369 a.a.

Struc: 398 a.a.*

* PDB and UniProt seqs differ at 41 residue positions (black crosses)

Chem Biol 14:909-922 (2007)

PubMed id: 17719490

Structural engineering of pMHC reagents for T cell vaccines and diagnostics.

V.Mitaksov, S.M.Truscott, L.Lybarger, J.M.Connolly, T.H.Hansen, D.H.Fremont.

ABSTRACT

MHC class I peptide complexes (pMHC) are routinely used to enumerate T cell populations and are currently being evaluated as vaccines to tumors and specific pathogens. Herein, we describe the structures of three generations of single-chain pMHC progressively designed for the optimal presentation of covalently associated epitopes. Our ultimate design employs a versatile disulfide trap between an invariant MHC residue and a short C-terminal peptide extension. This general strategy is nondisruptive of native pMHC conformation and T cell receptor engagement. Indeed, cell-surface-expressed MHC complexes with disulfide-trapped epitopes are refractory to peptide exchange, suggesting they will make safe and effective vaccines. Furthermore, we find that disulfide-trap stabilized, recombinant pMHC reagents reliably detect polyclonal CD8 T cell populations as proficiently as conventional reagents and are thus well suited to monitor or modulate immune responses during pathogenesis.