title: Structural analysis of mycobacterial and murine hsp60 epitopes in complex with the class I MHC molecule H-2Db.
abstract: The decameric peptide SALQNAASIA from the Mycobacterium bovis heat shock protein (hsp) 60 is recognized by the murine T-cell receptor UZ-3-4 in complex with the murine class I major histocompatibility complex molecule H-2D(b). This T-cell receptor cross-reacts with the H-2D(b)-bound non-homologous decameric peptide KDIGNIISDA from the murine hsp60, but does not recognize the nonameric mycobacterial peptide SALQNAASI. Cross-recognition of the KDIGNIISDA/H-2D(b) complex induces autoimmune pathology in immunodeficient mice. We solved the X-ray crystal structure of the SALQNAASIA/H-2D(b) complex at 3.0 A resolution, and we modelled the KDIGNIISDA and SALQNAASI peptides in the H-2D(b) binding site. The structural analysis of the H-2D(b)-bound hsp60 epitopes offers insight into T-cell receptor cross-reactivity.
authors.affiliation: Department of Biochemistry, University of Zürich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland.
authors.forename: Carlo
authors.initials: C
authors.lastname: Ciatto
authors.forename: Guido
authors.initials: G
authors.lastname: Capitani
authors.forename: Alain C
authors.initials: AC
authors.lastname: Tissot
authors.forename: Frédéric
authors.initials: F
authors.lastname: Pecorari
authors.forename: Andreas
authors.initials: A
authors.lastname: Plückthun
authors.forename: Markus G
authors.initials: MG
authors.lastname: Grütter
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry*; D001665:Binding Sites; D018834:Chaperonin 60 / Q000737:chemistry* / Q000276:immunology; D018360:Crystallography, X-Ray; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry*; D006183:H-2 Antigens / Q000737:chemistry* / Q000378:metabolism; D064532:Histocompatibility Antigen H-2D; D046911:Macromolecular Substances; D051379:Mice; D008958:Models, Molecular; D009163:Mycobacterium bovis / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry* / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D018834:Chaperonin 60; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D046911:Macromolecular Substances; D010446:Peptide Fragments