2clv: Difference between revisions
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New page: left|200px<br /><applet load="2clv" size="450" color="white" frame="true" align="right" spinBox="true" caption="2clv, resolution 1.90Å" /> '''MHC CLASS I NATURAL ... |
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[[Image:2clv.gif|left|200px]]<br /><applet load="2clv" size=" | [[Image:2clv.gif|left|200px]]<br /><applet load="2clv" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="2clv, resolution 1.90Å" /> | caption="2clv, resolution 1.90Å" /> | ||
'''MHC CLASS I NATURAL MUTANT H-2KBM8 HEAVY CHAIN COMPLEXED WITH BETA-2 MICROGLOBULIN AND PBM8 PEPTIDE'''<br /> | '''MHC CLASS I NATURAL MUTANT H-2KBM8 HEAVY CHAIN COMPLEXED WITH BETA-2 MICROGLOBULIN AND PBM8 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== | ||
2CLV 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:// | 2CLV 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=2CLV 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]] | ||
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[[Category: transmembrane]] | [[Category: transmembrane]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:49:58 2008'' | ||
