2ian
From Proteopedia
(New page: 200px<br /> <applet load="2ian" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ian, resolution 2.80Å" /> '''Structural basis fo...) |
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| - | [[Image:2ian.gif|left|200px]]<br /> | + | [[Image:2ian.gif|left|200px]]<br /><applet load="2ian" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2ian" size=" | + | |
caption="2ian, resolution 2.80Å" /> | caption="2ian, resolution 2.80Å" /> | ||
'''Structural basis for recognition of mutant self by a tumor-specific, MHC class II-restricted TCR'''<br /> | '''Structural basis for recognition of mutant self by a tumor-specific, MHC class II-restricted TCR'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Structural studies of complexes of T cell receptor (TCR) and peptide-major | + | Structural studies of complexes of T cell receptor (TCR) and peptide-major histocompatibility complex (MHC) have focused on TCRs specific for foreign antigens or native self. An unexplored category of TCRs includes those specific for self determinants bearing alterations resulting from disease, notably cancer. We determined here the structure of a human melanoma-specific TCR (E8) bound to the MHC molecule HLA-DR1 and an epitope from mutant triosephosphate isomerase. The structure had features intermediate between 'anti-foreign' and autoimmune TCR-peptide-MHC class II complexes that may reflect the hybrid nature of altered self. E8 manifested very low affinity for mutant triosephosphate isomerase-HLA-DR1 despite the highly tumor-reactive properties of E8 cells. A second TCR (G4) had even lower affinity but underwent peptide-specific formation of dimers, suggesting this as a mechanism for enhancing low-affinity TCR-peptide-MHC interactions for T cell activation. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2IAN is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Triose-phosphate_isomerase Triose-phosphate isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.1.1 5.3.1.1] Full crystallographic information is available from [http:// | + | 2IAN is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Triose-phosphate_isomerase Triose-phosphate isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.1.1 5.3.1.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IAN OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Triose-phosphate isomerase]] | [[Category: Triose-phosphate isomerase]] | ||
[[Category: Deng, L.]] | [[Category: Deng, L.]] | ||
| - | [[Category: Langley, R | + | [[Category: Langley, R J.]] |
| - | [[Category: Mariuzza, R | + | [[Category: Mariuzza, R A.]] |
[[Category: major histocompatibility complex]] | [[Category: major histocompatibility complex]] | ||
[[Category: melanoma]] | [[Category: melanoma]] | ||
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[[Category: x-ray crystallography]] | [[Category: x-ray crystallography]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:50:42 2008'' |
Revision as of 15:50, 21 February 2008
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Structural basis for recognition of mutant self by a tumor-specific, MHC class II-restricted TCR
Contents |
Overview
Structural studies of complexes of T cell receptor (TCR) and peptide-major histocompatibility complex (MHC) have focused on TCRs specific for foreign antigens or native self. An unexplored category of TCRs includes those specific for self determinants bearing alterations resulting from disease, notably cancer. We determined here the structure of a human melanoma-specific TCR (E8) bound to the MHC molecule HLA-DR1 and an epitope from mutant triosephosphate isomerase. The structure had features intermediate between 'anti-foreign' and autoimmune TCR-peptide-MHC class II complexes that may reflect the hybrid nature of altered self. E8 manifested very low affinity for mutant triosephosphate isomerase-HLA-DR1 despite the highly tumor-reactive properties of E8 cells. A second TCR (G4) had even lower affinity but underwent peptide-specific formation of dimers, suggesting this as a mechanism for enhancing low-affinity TCR-peptide-MHC interactions for T cell activation.
Disease
Known diseases associated with this structure: Hemolytic anemia due to triosephosphate isomerase deficiency OMIM:[190450]
About this Structure
2IAN is a Protein complex structure of sequences from Homo sapiens. Active as Triose-phosphate isomerase, with EC number 5.3.1.1 Full crystallographic information is available from OCA.
Reference
Structural basis for the recognition of mutant self by a tumor-specific, MHC class II-restricted T cell receptor., Deng L, Langley RJ, Brown PH, Xu G, Teng L, Wang Q, Gonzales MI, Callender GG, Nishimura MI, Topalian SL, Mariuzza RA, Nat Immunol. 2007 Apr;8(4):398-408. Epub 2007 Mar 4. PMID:17334368
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