2CLV

MHC Class I Natural Mutant H-2Kbm8 Heavy Chain Complexed With beta-2 Microglobulin and pBM8 peptide

2CLV の概要

• エントリーDOI: 10.2210/pdb2clv/pdb
• 関連するPDBエントリー: 1BQH 1FO0 1FZJ 1FZK 1FZM 1FZO 1G6R 1G7P 1G7Q 1KBG 1KJ2 1KJ3 1KPU 1KPV 1LEG 1LEK 1LK2 1MWA 1N59 1NAM 1NAN 1OSZ 1P1Z 1P4L 1RJY 1RJZ 1RK0 1RK1 1S7Q 1S7R 1S7S 1S7T 1T0M 1T0N 1VAC 1VAD 1WBZ 2CKB 2CLZ 2MHA 2VAA 2VAB
• 分子名称: H-2 CLASS I HISTOCOMPATIBILITY ANTIGEN, K-B ALPHA CHAIN, BETA-2 MICROGLOBULIN, RBM5 PROTEIN, ... (4 entities in total)
• 機能のキーワード: immune response, immune system, immunoglobulin domain, glycoprotein, transmembrane, alloreactivity, mhc i, h-2kbm8, membrane, class i mhc, polymorphism
• 由来する生物種: MUS MUSCULUS (MOUSE); 詳細
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P01901; Secreted: P01887
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 89640.48

構造登録者

Mazza, C.,Auphan-Anezin, N.,Guimezanes, A.,Barrett-Wilt, G.A.,Montero-Julian, F.,Roussel, A.,Hunt, D.F.,Schmitt-Verhulst, A.M.,Malissen, B. (登録日: 2006-05-02, 公開日: 2006-06-14, 最終更新日: 2024-11-06)

主引用文献

Auphan-Anezin, N.,Mazza, C.,Guimezanes, A.,Barrett-Wilt, G.A.,Montero-Julian, F.,Roussel, A.,Hunt, D.F.,Malissen, B.,Schmitt-Verhulst, A.M.
Distinct orientation of the alloreactive monoclonal CD8 T cell activation program by three different peptide/MHC complexes.
Eur. J. Immunol., 36:1856-1866, 2006

PubMed Abstract: 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.

PubMed: 16761314
DOI: 10.1002/eji.200635895

実験手法

X-RAY DIFFRACTION (1.9 Å)