3PL6

Structure of Autoimmune TCR Hy.1B11 in complex with HLA-DQ1 and MBP 85-99

Summary for 3PL6

• Entry DOI: 10.2210/pdb3pl6/pdb
• Related: 1YMM
• Descriptor: MHC class II HLA-DQ-alpha chain, MHC class II HLA-DQ-beta chain, T-cell receptor alpha chain, ... (6 entities in total)
• Functional Keywords: tcr-mhc complex, immunoglobulin fold, immune receptor, membrane, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 98356.15

Authors

Sethi, D.K.,Wucherpfennig, K.W. (deposition date: 2010-11-13, release date: 2010-12-22, Last modification date: 2024-10-30)

Primary citation

Sethi, D.K.,Schubert, D.A.,Anders, A.K.,Heroux, A.,Bonsor, D.A.,Thomas, C.P.,Sundberg, E.J.,Pyrdol, J.,Wucherpfennig, K.W.
A highly tilted binding mode by a self-reactive T cell receptor results in altered engagement of peptide and MHC.
J.Exp.Med., 208:91-102, 2011

PubMed Abstract: Self-reactive T cells that escape elimination in the thymus can cause autoimmune pathology, and it is therefore important to understand the structural mechanisms of self-antigen recognition. We report the crystal structure of a T cell receptor (TCR) from a patient with relapsing-remitting multiple sclerosis that engages its self-peptide-major histocompatibility complex (pMHC) ligand in an unusual manner. The TCR is bound in a highly tilted orientation that prevents interaction of the TCR-α chain with the MHC class II β chain helix. In this structure, only a single germline-encoded TCR loop engages the MHC protein, whereas in most other TCR-pMHC structures all four germline-encoded TCR loops bind to the MHC helices. The tilted binding mode also prevents peptide contacts by the short complementarity-determining region (CDR) 3β loop, and interactions that contribute to peptide side chain specificity are focused on the CDR3α loop. This structure is the first example in which only a single germline-encoded TCR loop contacts the MHC helices. Furthermore, the reduced interaction surface with the peptide may facilitate TCR cross-reactivity. The structural alterations in the trimolecular complex are distinct from previously characterized self-reactive TCRs, indicating that there are multiple unusual ways for self-reactive TCRs to bind their pMHC ligand.

PubMed: 21199956
DOI: 10.1084/jem.20100725

Experimental method

X-RAY DIFFRACTION (2.55 Å)