2CLZ

Mhc Class I Natural Mutant H-2Kbm8 Heavy Chain Complexed With beta-2 Microglobulin and pBM1 peptide

Summary for 2CLZ

• Entry DOI: 10.2210/pdb2clz/pdb
• Related: 1A1M 1A1N 1A1O 1AKJ 1B3J 1BD2 1BII 1CE6 1DDH 1FO0 1FYT 1FZJ 1FZK 1FZM 1FZO 1G7P 1G7Q 1HA5 1HQR 1HXY 1ICF 1IIE 1IM3 1J8H 1JE6 1JWM 1JWS 1JWU 1K2D 1K8D 1KBG 1KG0 1KJ2 1KJ3 1KJM 1KJV 1KPU 1KPV 1LDP 1LO5 1MHC 1NAM 1OSZ 1P1Z 1QLF 1QO3 1RJY 1RJZ 1RK0 1RK1 1SEB 1VAC 1VAD 1WBX 1WBY 1WBZ 1YN6 1YN7 1ZS8 2CII 2CLV 2CLZ 2F74 2FWO 2VAA 2VAB
• Descriptor: H-2 CLASS I HISTOCOMPATIBILITY ANTIGEN, K-B ALPHA CHAIN, BETA-2 MICROGLOBULIN, RBM5 PROTEIN, ... (4 entities in total)
• Functional Keywords: immune response, immune system, immunoglobulin domain, glycoprotein, transmembrane, alloreactivity, mhc i, h-2kbm8, membrane, class i mhc, polymorphism
• Biological source: MUS MUSCULUS (MOUSE); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01901; Secreted: P01887
• Total number of polymer chains: 6
• Total formula weight: 89532.47

Authors

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. (deposition date: 2006-05-03, release date: 2006-06-14, Last modification date: 2024-11-13)

Primary citation

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-, 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

Experimental method

X-RAY DIFFRACTION (1.9 Å)