title: Lipoprotein from Yersinia enterocolitica contains epitopes that cross-react with the human thyrotropin receptor.
abstract: Yersinia enterocolitica has recently been shown to produce a low molecular mass envelope protein that contains an epitope(s) that is cross-reactive with the extracellular domain of the human thyrotropin receptor (ETSHR). In this study, we have generated mAb to this cross-reactive protein and have obtained amino acid sequences for peptide fragments obtained from Lys-c digestion of the protein. The amino acid sequences of these peptides were identical to sequences present in bacterial lipoprotein (LP). All bacteria of the Enterobacteriaceae family produce LP as a major outer membrane protein. However, the ETSHR cross-reactive epitope(s) was shown to be unique to LP produced by Yersinia species. This was shown by Western blot analysis using a mAb specific for LP and with affinity-purified Ab specific for either LP or ETSHR and obtained from mouse antiserum generated to Y. enterocolitica. LPs from different Gram-negative bacteria were shown to be mitogenic for C3H/HeJ spleen cells and induced production and secretion of significant levels of Ig. Production of Ab that recognized the ETSHR was only induced in spleen cells stimulated with the LP obtained from Yersinia. In contrast, LP was not mitogenic for either human PBMC or human B cells. However, LP did induce IL6 and IL8 production in human monocytes at levels equivalent to that seen after LPS activation. These results identify, for the first time, the Yersinia envelope protein that is cross-reactive with the ETSHR and show that it can activate human monocytes. These findings are potentially important for advancing our understanding of the role molecular mimicry plays in the induction of autoimmunity to the thyrotropin receptor.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston 77555, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: I
authors.initials: I
authors.lastname: Kaur
authors.forename: D W
authors.initials: DW
authors.lastname: Niesel
authors.forename: G S
authors.initials: GS
authors.lastname: Seetharamaiah
authors.forename: J W
authors.initials: JW
authors.lastname: Peterson
authors.forename: B S
authors.initials: BS
authors.lastname: Prabhakar
authors.forename: G R
authors.initials: GR
authors.lastname: Klimpel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology*; D005110:Extracellular Space / Q000276:immunology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008074:Lipoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000494:pharmacology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009000:Monocytes / Q000378:metabolism; D011989:Receptors, Thyrotropin / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D015008:Yersinia enterocolitica / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D000939:Epitopes; D015850:Interleukin-6; D016209:Interleukin-8; D008074:Lipoproteins; D008934:Mitogens; D011989:Receptors, Thyrotropin