Unusual Features of Self-Peptide/MHC Binding by Autoimmune T Cell Receptors

摘要: Structural studies on T cell receptors (TCRs) specific for foreign antigens demonstrated a remarkably similar topology characterized by central, diagonal TCR binding mode that maximizes interactions with the MHC bound peptide. However, three recent structures involving autoimmune TCRs unusual self-peptide/MHC complexes. Two from multiple sclerosis patients bind unconventional topologies, and both are shifted toward peptide N terminus class II β chain helix. A experimental encephalomyelitis (EAE) model binds in conventional orientation, but structure is because self-peptide only partially fills site. For all TCRs, interaction suboptimal, two or loops contact Optimal modes confer competitive advantage antimicrobial cells during an infection, whereas altered properties may permit survival of subset autoreactive thymic selection.