2clz

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spinqualitylabelsall models 2clz, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

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