Identification of the predominant antigenic epitopes in intestinal flora in IBD

Abstract

The normal intestinal flora is required for the development of intestinal inflammation in animal models of inflammatory bowel disease (IBD). In humans, several studies indicated a potential association of Escherichia coli (E. coli) with IBD. In addition, we have shown that T-cell clones of IBD patients cross react toward different enteric bacterial species and thus likely respond to conserved bacterial antigens. Therefore, we hypothesized that highly conserved E. coli proteins might be a reasonable candidate to screen for abnormal T-cell responses in IBD. We used high-throughput techniques for cloning, expression, and purification under native conditions of a set of 271 conserved proteins of E. coli, of which 196 were used for whole blood stimulations to assess peripheral T helper (T(H))-cell responses. In addition, because of the association of an adherent-invasive E. coli with Crohn's disease (CD), we included 13 pathogenicity factors of E. coli in the study. We observed that pools of these conserved E. coli proteins less frequently induced interferon-gamma (IFNgamma) production in peripheral T(H) cells in patients with CD and ankylosing spondylitis (AS) compared with healthy controls. In addition, lower percentage of patients with CD and AS responded toward single proteins. The reason for the decreased frequency of an in vitro T(H)-cell IFNgamma response toward E. coli proteins in peripheral blood of CD and AS patients, e.g., increased suppression needs to be clarified.

Identification and Phylogeny of the First T Cell Epitope Identified from a Human Gut Bacteroides Species

“…[ 2 ] showed that individual T cell clones from IBD patients were reactive to Bacteroides thetaiotaomicron , Bifidobacterium bifidum , Escherichia coli , and Yersinia enterocolitica . In 2008, Duchmann and colleagues [ 3 ] expanded their studies on antigenic epitopes by screening T helper cells from healthy subjects and from patients with Crohn’s disease and ankylosing spondylitis. However, none of these studies identified the actual epitope that stimulate the T cell.…”

T-cell-directed therapies in inflammatory bowel diseases

“…studies conducted in various mouse models of IBDs have shown that most immunoregulatory events in mucosal inflammation are controlled by T-cells, that mucosal T-cell activation is antigen-dependent and the responsible antigens originate from intestinal bacteria [6][7][8]. MadCAM-1 and ICAM-1) on vascular endothelium and integrins (e.g.…”

Gatekeepers of intestinal inflammation

“…Dysregulated responses to ingested food is perhaps more clearly revealed in patients with celiac disease-where patients with the risk haplotype exhibit an uncontrolled sensitivity to gluten antigens resulting in intestinal inflammation, villous atrophy, and crypt hyperplasia [20]. In IBD, the antigen provoking the exacerbated and uncontrolled inflammatory response is not known, although there is some evidence suggesting that Crohn's disease patients may have lost tolerance to their own commensal bacterial flora [21,22]. Loss of tolerance to autologous flora could be a primary defect or arise simply as a secondary effect following some other dysregulated inflammatory stimulus or barrier function defect in the intestine.…”