Epitopes described in "How a single T cell receptor recognizes both self and foreign MHC."

Article Authors:Leremy A Colf; Alexander J Bankovich; Nicole A Hanick; Natalie A Bowerman; Lindsay L Jones; David M Kranz; K Christopher Garcia
Article Title:How a single T cell receptor recognizes both self and foreign MHC.
Reference Detail
Reference ID:1019712
Abstract:alphabeta T cell receptors (TCRs) can crossreact with both self- and foreign- major histocompatibility complex (MHC) proteins in an enigmatic phenomenon termed alloreactivity. Here we present the 2.35 A structure of the 2C TCR complexed with its foreign ligand H-2L(d)-QL9. Surprisingly, we find that this TCR utilizes a different strategy to engage the foreign pMHC in comparison to the manner in which it recognizes a self ligand H-2K(b)-dEV8. 2C engages both shared and polymorphic residues on L(d) and K(b), as well as the unrelated QL9 and dEV8 peptide antigens, in unique pair-wise contacts, resulting in greater structural complementarity with the L(d)-QL9 complex. In the structure of an engineered, high-affinity 2C TCR variant bound to H-2L(d)-QL9, the "wild-type" TCR-MHC binding orientation persists despite modified TCR-CDR3alpha interactions with peptide. Thus, a single TCR recognizes two globally similar, but distinct ligands by divergent mechanisms, indicating that receptor-ligand crossreactivity can occur in the absence of molecular mimicry.
Affiliations:Howard Hughes Medical Institute, Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Reference Type:Literature
PubMed ID:17418792
Journal Volume:129
Article Pages:135-46
Journal ISSN:0092-8674
Article Chemical List:Autoantigens;Complementarity Determining Regions;H-2 Antigens;H-2Kb protein, mouse;Histocompatibility Antigen H-2D;Isoantigens;Ligands;Peptides;Receptors, Antigen, T-Cell, alpha-beta;Ketoglutarate Dehydrogenase Complex
Article MeSH List:Amino Acid Sequence; Autoantigens(chemistry; immunology; metabolism); Complementarity Determining Regions(metabolism); Crystallography, X-Ray; H-2 Antigens(chemistry; immunology; metabolism); Histocompatibility Antigen H-2D; Isoantigens(chemistry; immunology; metabolism); Ketoglutarate Dehydrogenase Complex(chemistry; immunology); Ligands; Models, Molecular; Molecular Sequence Data; Peptides(chemistry; immunology; metabolism); Protein Binding; Receptors, Antigen, T-Cell, alpha-beta(chemistry; immunology; metabolism)
Curation Last Updated:2015-07-30 20:36:11