2FO4

Enhanced MHC class I binding and immune responses through anchor modification of the non-canonical tumor associated MUC1-8 peptide

Summary for 2FO4

• Entry DOI: 10.2210/pdb2fo4/pdb
• Related: 1G7Q
• Descriptor: H-2 class I histocompatibility antigen, K-B alpha chain, Beta-2-microglobulin, 8-mer from Mucin-1, ... (8 entities in total)
• Functional Keywords: anchor modifications, h-2kb, muc1, non-canonical peptide, muc1-8, vaccine design, immune system
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 3
• Total formula weight: 45506.89

Authors

Lazoura, E.,Ramsland, P.A. (deposition date: 2006-01-12, release date: 2006-11-14, Last modification date: 2024-10-23)

Primary citation

Lazoura, E.,Lodding, J.,Farrugia, W.,Ramsland, P.A.,Stevens, J.,Wilson, I.A.,Pietersz, G.A.,Apostolopoulos, V.
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, 2006

PubMed 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).

PubMed: 17067310
DOI: 10.1111/j.1365-2567.2006.02434.x

Experimental method

X-RAY DIFFRACTION (2.7 Å)