2ial

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(New page: 200px<br /><applet load="2ial" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ial, resolution 1.92&Aring;" /> '''Structural basis for...)
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[[Image:2ial.jpg|left|200px]]<br /><applet load="2ial" size="450" color="white" frame="true" align="right" spinBox="true"
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[[Image:2ial.jpg|left|200px]]<br /><applet load="2ial" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2ial, resolution 1.92&Aring;" />
caption="2ial, resolution 1.92&Aring;" />
'''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==
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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.
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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.
==About this Structure==
==About this Structure==
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2IAL is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2IAL OCA].
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2IAL is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IAL OCA].
==Reference==
==Reference==
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[[Category: Protein complex]]
[[Category: Protein complex]]
[[Category: Deng, L.]]
[[Category: Deng, L.]]
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[[Category: Langley, R.J.]]
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[[Category: Langley, R J.]]
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[[Category: Mariuzza, R.A.]]
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[[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]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 12:12:52 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:50:37 2008''

Revision as of 15:50, 21 February 2008


2ial, resolution 1.92Å

Drag the structure with the mouse to rotate

Structural basis for recognition of mutant self by a tumor-specific, MHC class II-restricted TCR

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.

About this Structure

2IAL is a Protein complex structure of sequences from Homo sapiens. 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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