PDBsum entry 2fo4

Immune system

PDB id: 2fo4

Contents

Protein chains

274 a.a. *

99 a.a. *

Ligands

SER-ALA-PRO-ASP-PHE-ARG-PRO-LEU

NAG-FUC

NAG

PO4 ×2

MPD ×4

Waters ×103

* Residue conservation analysis

PDB id:

2fo4

Name:

Immune system

Title:

Enhanced mhc class i binding and immune responses through anchor modification of the non-canonical tumor associated muc1-8 peptide

Structure:

H-2 class i histocompatibility antigen, k-b alpha chain. Chain: a. Fragment: extracellular domains, residues 1-274. Synonym: h-2kb. Engineered: yes. Beta-2-microglobulin. Chain: b. Engineered: yes. 8-mer from mucin-1.

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227. Synthetic: yes. Other_details: the 8-residue peptide of mucin 1 was chemically synthesized.

Biol. unit:

Trimer (from PQS)

Resolution:

2.70Å R-factor: 0.193 R-free: 0.248

Authors:

E.Lazoura,P.A.Ramsland

Key ref:

E.Lazoura et al. (2006). Enhanced major histocompatibility complex class I binding and immune responses through anchor modification of the non-canonical tumour-associated mucin 1-8 peptide. Immunology, 119, 306-316. PubMed id: 17067310

Date:

12-Jan-06 Release date: 14-Nov-06

Protein chain

Q3UBW0  (Q3UBW0_MOUSE) -  Ig-like domain-containing protein from Mus musculus

Seq: 347 a.a.

Struc: 274 a.a.

Protein chain

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)

Immunology 119:306-316 (2006)

PubMed id: 17067310

Enhanced major histocompatibility complex class I binding and immune responses through anchor modification of the non-canonical tumour-associated mucin 1-8 peptide.

E.Lazoura, J.Lodding, W.Farrugia, P.A.Ramsland, J.Stevens, I.A.Wilson, G.A.Pietersz, V.Apostolopoulos.

ABSTRACT

Designing peptide-based vaccines for therapeutic applications in cancer immunotherapy requires detailed knowledge of the interactions between the antigenic peptide and major histocompatibility complex (MHC) in addition to that between the peptide-MHC complex and the T-cell receptor. Past efforts to immunize with high-affinity tumour-associated antigenic peptides have not been very immunogenic, which may be attributed to the lack of T cells to these peptides, having been deleted during thymic development. For this reason, low-to-medium affinity non-canonical peptides represent more suitable candidates. However, in addition to the difficulty in identifying such antigens, peptide binding to MHC, and hence its ability to induce a strong immune response, is limited. Therefore, to enhance binding to MHC and improve immune responses, anchor modifications of non-canonical tumour-associated peptides would be advantageous. In this study, the non-canonical tumour-associated peptide from MUC1, MUC1-8 (SAPDTRPA), was modified at the MHC anchor residues to SAPDFRPL (MUC1-8-5F8L) and showed enhanced binding to H-2Kb and improved immune responses. Furthermore, the crystal structure of MUC1-8-5F8L in complex with H-2Kb was determined and it revealed that binding of the peptide to MHC is similar to that of the canonical peptide OVA8 (SIINFEKL).