LIPOPROTEIN FROM YERSINIA-ENTEROCOLITICA CONTAINS EPITOPES THAT CROSS-REACT WITH THE HUMAN THYROTROPIN RECEPTOR

Yersinia enterocolitica has recently been shown to produce a low molec ular mass envelope protein that contains an epitope(s) that is cross-r eactive with the extracellular domain of the human thyrotropin recepto r (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 li poprotein (LP). All bacteria of the Enterobacteriaceae family produce LP as a major outer membrane protein. However, the ETSHR cross-reactiv e 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 obta ined from mouse antiserum generated to Y. enterocolitica. LPs from dif ferent Gram-negative bacteria were shown to be mitogenic for C3H/HeJ s pleen 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 contra st, LP was not mitogenic for either human PBMC or human B cells. Howev er, LP did induce IL6 and Its production in human monocytes at levers equivalent to that seen after LPS activation. These results identify, for the first time, the Yersinia envelope protein that is cross-reacti ve 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 prays in the induction of autoimmunity to the thyrotropin receptor.