PDBsum entry 4grl

Immune system

PDB id: 4grl

Contents

Protein chains

182 a.a.

181 a.a.

191 a.a.

257 a.a.

Ligands

NAG

Waters ×35

PDB id:

4grl

Name:

Immune system

Title:

Crystal structure of a autoimmune tcr-mhc complex

Structure:

Mhc class ii hla-dq-alpha chain. Chain: a. Engineered: yes. Mhc class ii antigen. Chain: b. Engineered: yes. Tcr hy.1b11 alpha chain. Chain: c. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: alpha chain, hla-dq1, hla-dqa1, mhc class ii molecule. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Gene: beta chain, hla-dq1, hla-dqb1, mhc class ii molecule. Gene: tcr hy.1b11 alpha chain. Expressed in: escherichia coli.

Resolution:

2.86Å R-factor: 0.204 R-free: 0.256

Authors:

D.K.Sethi,K.W.Wucherpfennig

Key ref:

D.K.Sethi et al. (2013). Crossreactivity of a human autoimmune TCR is dominated by a single TCR loop. Nat Commun, 4, 2623. PubMed id: 24136005 DOI: 10.1038/ncomms3623

Date:

25-Aug-12 Release date: 06-Nov-13

Protein chain

Q30066  (Q30066_HUMAN) -  MHC class II HLA-DQ-alpha chain (Fragment) from Homo sapiens

Seq: 227 a.a.

Struc: 182 a.a.

Protein chain

Q67AJ6  (Q67AJ6_HUMAN) -  MHC class II antigen (Fragment) from Homo sapiens

Seq: 234 a.a.

Struc: 181 a.a.

Protein chain

No UniProt id for this chain

Struc: 191 a.a.

Protein chain

No UniProt id for this chain

Struc: 257 a.a.

DOI no: 10.1038/ncomms3623

Nat Commun 4:2623 (2013)

PubMed id: 24136005

Crossreactivity of a human autoimmune TCR is dominated by a single TCR loop.

D.K.Sethi, S.Gordo, D.A.Schubert, K.W.Wucherpfennig.

ABSTRACT

Self-reactive CD4 T cells are thought to have a central role in the pathogenesis of many chronic inflammatory human diseases. Microbial peptides can activate self-reactive T cells, but the structural basis for such crossreactivity is not well understood. The Hy.1B11 T cell receptor (TCR) originates from a patient with multiple sclerosis and recognizes the self-antigen myelin basic protein. Here we report the structural mechanism of TCR crossreactivity with two distinct peptides from human pathogens. The structures show that a single TCR residue (CDR3α F95) makes the majority of contacts with the self-peptide and both microbial peptides (66.7-80.6%) due to a highly tilted TCR-binding topology on the peptide-MHC surface. Further, a neighbouring residue located on the same TCR loop (CDR3α E98) forms an energetically critical interaction with the MHC molecule. These data show how binding by a self-reactive TCR favors crossreactivity between self and microbial antigens.