1klu
From Proteopedia
(New page: 200px<br /> <applet load="1klu" size="450" color="white" frame="true" align="right" spinBox="true" caption="1klu, resolution 1.93Å" /> '''Crystal structure o...) |
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| - | [[Image:1klu.gif|left|200px]]<br /> | + | [[Image:1klu.gif|left|200px]]<br /><applet load="1klu" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1klu" size=" | + | |
caption="1klu, resolution 1.93Å" /> | caption="1klu, resolution 1.93Å" /> | ||
'''Crystal structure of HLA-DR1/TPI(23-37) complexed with staphylococcal enterotoxin C3 variant 3B2 (SEC3-3B2)'''<br /> | '''Crystal structure of HLA-DR1/TPI(23-37) complexed with staphylococcal enterotoxin C3 variant 3B2 (SEC3-3B2)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | While most immunotherapies for cancer have focused on eliciting specific | + | While most immunotherapies for cancer have focused on eliciting specific CD8+ cytotoxic T lymphocyte killing of tumor cells, a mounting body of evidence suggests that stimulation of anti-tumor CD4+ T cell help may be required for highly effective therapy. Several MHC class II-restricted tumor antigens that specifically activate such CD4+ helper T lymphocytes have now been identified, including one from a melanoma tumor that is caused by a single base-pair mutation in the glycolytic enzyme triosephosphate isomerase. This mutation results in the conversion of a threonine residue to isoleucine within the antigenic epitope, concomitant with a greater than five log-fold increase in stimulation of a CD4+ tumor-infiltrating lymphocyte line. Here, we present the crystal structures of HLA-DR1 in complex with both wild-type and mutant TPI peptide antigens, the first structures of tumor peptide antigen/MHC class II complexes recognized by CD4+ T cells to be reported. These structures show that very minor changes in the binding surface for T cell receptor correspond to the dramatic differences in T cell stimulation. Defining the structural basis by which CD4+ T cell help is invoked in an anti-tumor immune response will likely aid the design of more effective cancer immunotherapies. |
==About this Structure== | ==About this Structure== | ||
| - | 1KLU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http:// | + | 1KLU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KLU OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Staphylococcus aureus]] | [[Category: Staphylococcus aureus]] | ||
| - | [[Category: Andersen, P | + | [[Category: Andersen, P S.]] |
| - | [[Category: Mariuzza, R | + | [[Category: Mariuzza, R A.]] |
| - | [[Category: Sawicki, M | + | [[Category: Sawicki, M W.]] |
[[Category: Sette, A.]] | [[Category: Sette, A.]] | ||
[[Category: Sidney, J.]] | [[Category: Sidney, J.]] | ||
| - | [[Category: Sundberg, E | + | [[Category: Sundberg, E J.]] |
[[Category: cd4+ t cells]] | [[Category: cd4+ t cells]] | ||
[[Category: enterotoxin c3]] | [[Category: enterotoxin c3]] | ||
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[[Category: human melanoma antigen]] | [[Category: human melanoma antigen]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:35:30 2008'' |
Revision as of 11:35, 21 February 2008
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Crystal structure of HLA-DR1/TPI(23-37) complexed with staphylococcal enterotoxin C3 variant 3B2 (SEC3-3B2)
Overview
While most immunotherapies for cancer have focused on eliciting specific CD8+ cytotoxic T lymphocyte killing of tumor cells, a mounting body of evidence suggests that stimulation of anti-tumor CD4+ T cell help may be required for highly effective therapy. Several MHC class II-restricted tumor antigens that specifically activate such CD4+ helper T lymphocytes have now been identified, including one from a melanoma tumor that is caused by a single base-pair mutation in the glycolytic enzyme triosephosphate isomerase. This mutation results in the conversion of a threonine residue to isoleucine within the antigenic epitope, concomitant with a greater than five log-fold increase in stimulation of a CD4+ tumor-infiltrating lymphocyte line. Here, we present the crystal structures of HLA-DR1 in complex with both wild-type and mutant TPI peptide antigens, the first structures of tumor peptide antigen/MHC class II complexes recognized by CD4+ T cells to be reported. These structures show that very minor changes in the binding surface for T cell receptor correspond to the dramatic differences in T cell stimulation. Defining the structural basis by which CD4+ T cell help is invoked in an anti-tumor immune response will likely aid the design of more effective cancer immunotherapies.
About this Structure
1KLU is a Protein complex structure of sequences from Homo sapiens and Staphylococcus aureus. Full crystallographic information is available from OCA.
Reference
Minor structural changes in a mutated human melanoma antigen correspond to dramatically enhanced stimulation of a CD4+ tumor-infiltrating lymphocyte line., Sundberg EJ, Sawicki MW, Southwood S, Andersen PS, Sette A, Mariuzza RA, J Mol Biol. 2002 May 31;319(2):449-61. PMID:12051920
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