Structural highlights
Publication Abstract from PubMed
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-alpha chain with the MHC class II beta 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) 3beta loop, and interactions that contribute to peptide side chain specificity are focused on the CDR3alpha 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.
A highly tilted binding mode by a self-reactive T cell receptor results in altered engagement of peptide and MHC.,Sethi DK, Schubert DA, Anders AK, Heroux A, Bonsor DA, Thomas CP, Sundberg EJ, Pyrdol J, Wucherpfennig KW J Exp Med. 2011 Jan 17;208(1):91-102. Epub 2011 Jan 3. PMID:21199956[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sethi DK, Schubert DA, Anders AK, Heroux A, Bonsor DA, Thomas CP, Sundberg EJ, Pyrdol J, Wucherpfennig KW. A highly tilted binding mode by a self-reactive T cell receptor results in altered engagement of peptide and MHC. J Exp Med. 2011 Jan 17;208(1):91-102. Epub 2011 Jan 3. PMID:21199956 doi:10.1084/jem.20100725
