title: Structural alterations in peptide-MHC recognition by self-reactive T cell receptors.
abstract: The crystal structures of five autoimmune T cell receptor (TCR)-peptide-MHC complexes reveal substantial structural alterations compared to antimicrobial TCRs. The two human TCRs bind their self-peptide-MHC ligands with an altered topology, while the three mouse receptors recognize a self-peptide that only partially fills the MHC-binding groove. In most cases the peptide is contacted only by a subset of available TCR complementarity-determining loops and there is a paucity of hydrogen bonds from TCR to peptide. These suboptimal binding properties may have enabled escape from negative thymic selection. While only minute amounts of antigen are typically available for negative selection, the antigens recognized by many autoimmune TCRs are abundant in the target organ. Such compensatory mechanisms can allow self-reactive T cells with altered TCR-binding properties to be pathogenic.
authors.affiliation: Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. kai_wucherpfennig@dfci.harvard.edu
authors.forename: Kai W
authors.initials: KW
authors.lastname: Wucherpfennig
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Call
authors.forename: Lu
authors.initials: L
authors.lastname: Deng
authors.forename: Roy
authors.initials: R
authors.lastname: Mariuzza
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D015551:Autoimmunity; D006649:Histocompatibility Antigens / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D008024:Ligands; D010455:Peptides / Q000737:chemistry* / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000276:immunology*
chemical_list: D001324:Autoantigens; D006649:Histocompatibility Antigens; D008024:Ligands; D010455:Peptides; D011948:Receptors, Antigen, T-Cell
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