2clz

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{{STRUCTURE_2clz| PDB=2clz | SCENE= }}
{{STRUCTURE_2clz| PDB=2clz | SCENE= }}
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'''MHC CLASS I NATURAL MUTANT H-2KBM8 HEAVY CHAIN COMPLEXED WITH BETA-2 MICROGLOBULIN AND PBM1 PEPTIDE'''
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===MHC CLASS I NATURAL MUTANT H-2KBM8 HEAVY CHAIN COMPLEXED WITH BETA-2 MICROGLOBULIN AND PBM1 PEPTIDE===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 16761314 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16761314}}
==About this Structure==
==About this Structure==
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[[Category: Polymorphism]]
[[Category: Polymorphism]]
[[Category: Transmembrane]]
[[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 Sun Jul 27 23:18:51 2008''

Revision as of 20:18, 27 July 2008

Image:2clz.png

Template:STRUCTURE 2clz

MHC CLASS I NATURAL MUTANT H-2KBM8 HEAVY CHAIN COMPLEXED WITH BETA-2 MICROGLOBULIN AND PBM1 PEPTIDE

Template:ABSTRACT PUBMED 16761314

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

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