2clz

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[[Image:2clz.gif|left|200px]]
[[Image:2clz.gif|left|200px]]
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{{Structure
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{{STRUCTURE_2clz| PDB=2clz | SCENE= }}
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2clz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2clz OCA], [http://www.ebi.ac.uk/pdbsum/2clz PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2clz RCSB]</span>
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'''MHC CLASS I NATURAL MUTANT H-2KBM8 HEAVY CHAIN COMPLEXED WITH BETA-2 MICROGLOBULIN AND PBM1 PEPTIDE'''
'''MHC CLASS I NATURAL MUTANT H-2KBM8 HEAVY CHAIN COMPLEXED WITH BETA-2 MICROGLOBULIN AND PBM1 PEPTIDE'''
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[[Category: Roussel, A.]]
[[Category: Roussel, A.]]
[[Category: Schmitt-Verhulst, A M.]]
[[Category: Schmitt-Verhulst, A M.]]
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[[Category: alloreactivity]]
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[[Category: Alloreactivity]]
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[[Category: class i mhc]]
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[[Category: Class i mhc]]
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[[Category: glycoprotein]]
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[[Category: Glycoprotein]]
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[[Category: h-2kbm8]]
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[[Category: H-2kbm8]]
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[[Category: immune response]]
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[[Category: Immune response]]
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[[Category: immune system]]
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[[Category: Immune system]]
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[[Category: immunoglobulin domain]]
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[[Category: Immunoglobulin domain]]
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[[Category: membrane]]
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[[Category: Membrane]]
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[[Category: mhc i]]
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[[Category: Mhc i]]
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[[Category: polymorphism]]
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[[Category: Polymorphism]]
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[[Category: transmembrane]]
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[[Category: Transmembrane]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 22:28:02 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:23:20 2008''
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Revision as of 19:28, 3 May 2008

Image:2clz.gif

Template:STRUCTURE 2clz

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 Sat May 3 22:28:02 2008

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