title: Pfit is a structurally novel Crohn's disease-associated superantigen.
abstract: T cell responses to enteric bacteria are important in inflammatory bowel disease. I2, encoded by the pfiT gene of Pseudomonas fluorescens, is a T-cell superantigen associated with human Crohn's disease. Here we report the crystal structure of pfiT at 1.7Å resolution and provide a functional analysis of the interaction of pfiT and its homolog, PA2885, with human class II MHC. Both pfiT and PA2885 bound to mammalian cells and stimulated the proliferation of human lymphocytes. This binding was greatly inhibited by anti-class II MHC HLA-DR antibodies, and to a lesser extent, by anti HLA-DQ and DP antibodies, indicating that the binding was class II MHC-specific. GST-pfiT efficiently precipitated both endogenous and in vitro purified recombinant HLA-DR1 molecules, indicating that pfiT directly interacted with HLA-DR1. Competition studies revealed that pfiT and the superantigen Mycoplasma arthritidis mitogen (MAM) competed for binding to HLA-DR, indicating that their binding sites overlap. Structural analyses established that pfiT belongs to the TetR-family of DNA-binding transcription regulators. The distinct structure of pfiT indicates that it represents a new family of T cell superantigens.
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, New York, United States of America.
authors.forename: Lihui
authors.initials: L
authors.lastname: Liu
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, New York, United States of America.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, New York, United States of America.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Brecher
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, New York, United States of America.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America.
authors.forename: Bo
authors.initials: B
authors.lastname: Wei
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, New York, United States of America.
authors.forename: Bisweswar
authors.initials: B
authors.lastname: Nandi
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, New York, United States of America.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, New York, United States of America.
authors.forename: Hua
authors.initials: H
authors.lastname: Ling
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, New York, United States of America ; Department of Biomedical Sciences, School of Public Health, State University of New York, Albany, New York, United States of America.
authors.forename: Gary
authors.initials: G
authors.lastname: Winslow
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Braun
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, New York, United States of America ; Department of Biomedical Sciences, School of Public Health, State University of New York, Albany, New York, United States of America.
authors.forename: Hongmin
authors.initials: H
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D003424:Crohn Disease / Q000276:immunology*; D018360:Crystallography, X-Ray; D015798:HLA-DR1 Antigen / Q000378:metabolism; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011550:Pseudomonas aeruginosa / Q000276:immunology; D011551:Pseudomonas fluorescens / Q000276:immunology*; D017385:Sequence Homology; D018089:Superantigens / Q000737:chemistry* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D015798:HLA-DR1 Antigen; C469916:PfiT protein, Pseudomonas fluorescens; D018089:Superantigens