2fo4
From Proteopedia
(New page: 200px<br /> <applet load="2fo4" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fo4, resolution 2.70Å" /> '''Enhanced MHC class ...) |
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| - | [[Image:2fo4.gif|left|200px]]<br /> | + | [[Image:2fo4.gif|left|200px]]<br /><applet load="2fo4" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2fo4" size=" | + | |
caption="2fo4, resolution 2.70Å" /> | caption="2fo4, resolution 2.70Å" /> | ||
'''Enhanced MHC class I binding and immune responses through anchor modification of the non-canonical tumor associated MUC1-8 peptide'''<br /> | '''Enhanced MHC class I binding and immune responses through anchor modification of the non-canonical tumor associated MUC1-8 peptide'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Designing peptide-based vaccines for therapeutic applications in cancer | + | 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== | ==About this Structure== | ||
| - | 2FO4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with NAG, PO4 and MPD as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2FO4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=PO4:'>PO4</scene> and <scene name='pdbligand=MPD:'>MPD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FO4 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Lazoura, E.]] | [[Category: Lazoura, E.]] | ||
| - | [[Category: Ramsland, P | + | [[Category: Ramsland, P A.]] |
[[Category: MPD]] | [[Category: MPD]] | ||
[[Category: NAG]] | [[Category: NAG]] | ||
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[[Category: vaccine design]] | [[Category: vaccine design]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:23:23 2008'' |
Revision as of 15:23, 21 February 2008
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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 , and 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
Page seeded by OCA on Thu Feb 21 17:23:23 2008
Categories: Mus musculus | Protein complex | Lazoura, E. | Ramsland, P A. | MPD | NAG | PO4 | Anchor modifications | H-2kb | Muc1 | Muc1-8 | Non-canonical peptide | Vaccine design
