2fo4

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spinqualitylabelsall models 2fo4, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Overview

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).

About this Structure

2FO4 is a Protein complex structure of sequences from Mus musculus with NAG, PO4 and MPD as ligands. Full crystallographic information is available from OCA.

Reference

Enhanced major histocompatibility complex class I binding and immune responses through anchor modification of the non-canonical tumour-associated mucin 1-8 peptide., Lazoura E, Lodding J, Farrugia W, Ramsland PA, Stevens J, Wilson IA, Pietersz GA, Apostolopoulos V, Immunology. 2006 Nov;119(3):306-16. PMID:17067310

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