2clv: Difference between revisions

Revision as of 17:49, 21 February 2008

MHC CLASS I NATURAL MUTANT H-2KBM8 HEAVY CHAIN COMPLEXED WITH BETA-2 MICROGLOBULIN AND PBM8 PEPTIDE

OverviewOverview

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 StructureAbout this Structure

2CLV is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.

ReferenceReference

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 16:49:58 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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-[[Image:2clv.gif|left|200px]]<br /><applet load="2clv" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:2clv.gif|left|200px]]<br /><applet load="2clv" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="2clv, resolution 1.90&Aring;" />
 '''MHC CLASS I NATURAL MUTANT H-2KBM8 HEAVY CHAIN COMPLEXED WITH BETA-2 MICROGLOBULIN AND PBM8 PEPTIDE'''<br />
 ==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.
+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==
-CLV 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2CLV OCA].
+CLV 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==
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 [[Category: Protein complex]]
 [[Category: Auphan-Anezin, N.]]
-[[Category: Barrett-Wilt, G.A.]]
+[[Category: Barrett-Wilt, G A.]]
 [[Category: Guimezanes, A.]]
-[[Category: Hunt, D.F.]]
+[[Category: Hunt, D F.]]
 [[Category: Malissen, B.]]
 [[Category: Mazza, C.]]
 [[Category: Montero-Julian, F.]]
 [[Category: Roussel, A.]]
-[[Category: Schmitt-Verhulst, A.M.]]
+[[Category: Schmitt-Verhulst, A M.]]
 [[Category: alloreactivity]]
 [[Category: class i mhc]]
@@ Line 34: / Line 34: @@
 [[Category: transmembrane]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 09:09:55 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:49:58 2008''