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2clz
From Proteopedia
(New page: 200px<br /><applet load="2clz" size="450" color="white" frame="true" align="right" spinBox="true" caption="2clz, resolution 1.90Å" /> '''MHC CLASS I NATURAL ...) |
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| - | [[Image:2clz.gif|left|200px]]<br /><applet load="2clz" size=" | + | [[Image:2clz.gif|left|200px]]<br /><applet load="2clz" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2clz, resolution 1.90Å" /> | caption="2clz, resolution 1.90Å" /> | ||
'''MHC CLASS I NATURAL MUTANT H-2KBM8 HEAVY CHAIN COMPLEXED WITH BETA-2 MICROGLOBULIN AND PBM1 PEPTIDE'''<br /> | '''MHC CLASS I NATURAL MUTANT H-2KBM8 HEAVY CHAIN COMPLEXED WITH BETA-2 MICROGLOBULIN AND PBM1 PEPTIDE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | We have characterized three different programs of activation for | + | We have characterized three different programs of activation for alloreactive CD8 T cells expressing the BM3.3 TCR, their elicitation depending on the characteristics of the stimulating peptide/MHC complex. The high-affinity interaction between the TCR and the K(b)-associated endogenous peptide pBM1 (INFDFNTI) induced a complete differentiation program into effector cells correlated with sustained ERK activation. The K(bm8) variant elicited a partial activation program with delayed T cell proliferation, poor CTL activity and undetectable ERK phosphorylation; this resulted from a low-avidity interaction of TCR BM3.3 with a newly identified endogenous peptide, pBM8 (SQYYYNSL). Interestingly, mismatched pBM1/K(bm8) complexes induced a split response in BM3.3 T cells, with total reconstitution of T cell proliferation but defective generation of CTL activity that was correlated with strong but shortened ERK phosphorylation. Crystal structures highlight the molecular basis for the higher stability of pBM8/K(bm8) compared to pBM1/K(bm8) complexes that exist in two conformers. This study illustrates the importance of the stability of both peptide/MHC and peptide/MHC-TCR interactions for induction of sustained signaling required to induce optimal CTL effector functions. Subtle allelic structural variations, amplified by peptide selection, may thus orient distinct outcomes of alloreactive TCR-based therapies. |
==About this Structure== | ==About this Structure== | ||
| - | 2CLZ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http:// | + | 2CLZ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CLZ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Auphan-Anezin, N.]] | [[Category: Auphan-Anezin, N.]] | ||
| - | [[Category: Barrett-Wilt, G | + | [[Category: Barrett-Wilt, G A.]] |
[[Category: Guimezanes, A.]] | [[Category: Guimezanes, A.]] | ||
| - | [[Category: Hunt, D | + | [[Category: Hunt, D F.]] |
[[Category: Malissen, B.]] | [[Category: Malissen, B.]] | ||
[[Category: Mazza, C.]] | [[Category: Mazza, C.]] | ||
[[Category: Montero-Julian, F.]] | [[Category: Montero-Julian, F.]] | ||
[[Category: Roussel, A.]] | [[Category: Roussel, A.]] | ||
| - | [[Category: Schmitt-Verhulst, A | + | [[Category: Schmitt-Verhulst, A M.]] |
[[Category: alloreactivity]] | [[Category: alloreactivity]] | ||
[[Category: class i mhc]] | [[Category: class i mhc]] | ||
| Line 34: | Line 34: | ||
[[Category: transmembrane]] | [[Category: transmembrane]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:50:01 2008'' |
Revision as of 14:50, 21 February 2008
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MHC CLASS I NATURAL MUTANT H-2KBM8 HEAVY CHAIN COMPLEXED WITH BETA-2 MICROGLOBULIN AND PBM1 PEPTIDE
Overview
We have characterized three different programs of activation for alloreactive CD8 T cells expressing the BM3.3 TCR, their elicitation depending on the characteristics of the stimulating peptide/MHC complex. The high-affinity interaction between the TCR and the K(b)-associated endogenous peptide pBM1 (INFDFNTI) induced a complete differentiation program into effector cells correlated with sustained ERK activation. The K(bm8) variant elicited a partial activation program with delayed T cell proliferation, poor CTL activity and undetectable ERK phosphorylation; this resulted from a low-avidity interaction of TCR BM3.3 with a newly identified endogenous peptide, pBM8 (SQYYYNSL). Interestingly, mismatched pBM1/K(bm8) complexes induced a split response in BM3.3 T cells, with total reconstitution of T cell proliferation but defective generation of CTL activity that was correlated with strong but shortened ERK phosphorylation. Crystal structures highlight the molecular basis for the higher stability of pBM8/K(bm8) compared to pBM1/K(bm8) complexes that exist in two conformers. This study illustrates the importance of the stability of both peptide/MHC and peptide/MHC-TCR interactions for induction of sustained signaling required to induce optimal CTL effector functions. Subtle allelic structural variations, amplified by peptide selection, may thus orient distinct outcomes of alloreactive TCR-based therapies.
About this Structure
2CLZ is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
Reference
Distinct orientation of the alloreactive monoclonal CD8 T cell activation program by three different peptide/MHC complexes., Auphan-Anezin N, Mazza C, Guimezanes A, Barrett-Wilt GA, Montero-Julian F, Roussel A, Hunt DF, Malissen B, Schmitt-Verhulst AM, Eur J Immunol. 2006 Jul;36(7):1856-66. PMID:16761314
Page seeded by OCA on Thu Feb 21 16:50:01 2008
Categories: Mus musculus | Protein complex | Auphan-Anezin, N. | Barrett-Wilt, G A. | Guimezanes, A. | Hunt, D F. | Malissen, B. | Mazza, C. | Montero-Julian, F. | Roussel, A. | Schmitt-Verhulst, A M. | Alloreactivity | Class i mhc | Glycoprotein | H-2kbm8 | Immune response | Immune system | Immunoglobulin domain | Membrane | Mhc i | Polymorphism | Transmembrane
