PDBsum entry 2clz

Immune system

PDB id: 2clz

Contents

Protein chains

279 a.a. *

99 a.a. *

Ligands

ILE-ASN-PHE-ASP-PHE-ASN-THR-ILE ×2

Waters ×641

* Residue conservation analysis

PDB id:

2clz

Name:

Immune system

Title:

Mhc class i natural mutant h-2kbm8 heavy chain complexed with beta-2 microglobulin and pbm1 peptide

Structure:

H-2 class i histocompatibility antigen, k-b alpha chain. Chain: a, h. Fragment: extracellular domains (alpha1, alpha2, alpha3), residues 22-300. Synonym: h-2k(b). Engineered: yes. Mutation: yes. Beta-2 microglobulin. Chain: b, p.

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 511693. Synthetic: yes. Organism_taxid: 10090

Biol. unit:

Trimer (from PDB file)

Resolution:

1.90Å R-factor: 0.208 R-free: 0.247

Authors:

C.Mazza,N.Auphan-Anezin,A.Guimezanes,G.A.Barrett-Wilt,F.Montero- Julian,A.Roussel,D.F.Hunt,A.M.Schmitt-Verhulst,B.Malissen

Key ref:

N.Auphan-Anezin et al. (2006). Distinct orientation of the alloreactive monoclonal CD8 T cell activation program by three different peptide/MHC complexes. Eur J Immunol, 36, 1856-1866. PubMed id: 16761314 DOI: 10.1002/eji.200635895

Date:

03-May-06 Release date: 14-Jun-06

Protein chains

P01901  (HA1B_MOUSE) -  H-2 class I histocompatibility antigen, K-B alpha chain from Mus musculus

Seq: 369 a.a.

Struc: 279 a.a.*

Protein chains

P01887  (B2MG_MOUSE) -  Beta-2-microglobulin from Mus musculus

Seq: 119 a.a.

Struc: 99 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

DOI no: 10.1002/eji.200635895

Eur J Immunol 36:1856-1866 (2006)

PubMed id: 16761314

Distinct orientation of the alloreactive monoclonal CD8 T cell activation program by three different peptide/MHC complexes.

N.Auphan-Anezin, C.Mazza, A.Guimezanes, G.A.Barrett-Wilt, F.Montero-Julian, A.Roussel, D.F.Hunt, B.Malissen, A.M.Schmitt-Verhulst.

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.