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| [[Image:2clz.gif|left|200px]] | | {{Seed}} |
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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'''
| | ===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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_16761314}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16761314 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_16761314}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Polymorphism]] | | [[Category: Polymorphism]] |
| [[Category: Transmembrane]] | | [[Category: Transmembrane]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 22:28:02 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 23:18:51 2008'' |
