A highly tilted binding mode by a self-reactive T cell receptor results in altered engagement of peptide and MHC.

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 complem

SUBMITTER: Sethi DK 

PROVIDER: S-EPMC3023130 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature