Christopher L. Sutton

Pseudomonas fluorescens Encodes the Crohn's Disease-Associated I2 Sequence and T-Cell Superantigen

ABSTRACT Commensal bacteria have emerged as an important disease factor in human Crohns disease (CD) and murine inflammatory bowel disease (IBD) models. We recently isolated I2, a novel gene segment of microbial origin that is associated with human CD and that encodes a T-cell superantigen. To identify the I2 microorganism, BLAST analysis was used to identify a microbial homologue, PA2885, a novel open reading frame (ORF) in the Pseudomonas aeruginosa genome. PCR and Southern analysis identified Pseudomonas fluorescens as the originating species of I2, with homologues detectable in 3 of 13 other Pseudomonas species. Genomic cloning disclosed a locus containing the full-length I2 gene (pfiT) and three other orthologous genes, including a homologue of the pbrA/pvdS iron response gene. CD4+ T-cell responses to recombinant proteins were potent for I2 and pfiT, but modest for PA2885. pfiT has several features of a virulence factor: association with an iron-response locus, restricted species distribution, and T-cell superantigen bioactivity. These findings suggest roles for pfiT and P. fluorescens in the pathogenesis of Crohns disease.

The Crohn's disease-associated bacterial protein I2 is a novel enteric t cell superantigen.

Abstract An aberrant T cell response to enteric bacteria is important in inflammatory bowel disease. However, the identity of relevant microbial antigens is unknown. Here, we report the presence of I2, a Crohns disease-associated microbial gene, in the murine intestine. The I2 protein induced a proliferative and IL-10 response by CD4 + T cells from unimmunized mice. The I2 response was dependent on MHC class II-mediated recognition but did not require antigen processing. Selective activation was observed for the TCR-Vβ5 subpopulation. These findings indicate that the I2 protein is a new class of T cell superantigen and suggest that colonization by the I2 microorganism in susceptible hosts may provide a superantigenic stimulus pertinent to Crohns disease pathogenesis.

The Crohn's disease-associated bacterial protein, 12, is a novel enteric T cell superantigen

An aberrant T cell response to enteric bacteria is important in inflammatory bowel disease. However, the identity of relevant microbial antigens is unknown. Here, we report the presence of I2, a Crohns disease-associated microbial gene, in the murine intestine. The I2 protein induced a proliferative and IL-10 response by CD4(+) T cells from unimmunized mice. The I2 response was dependent on MHC class II-mediated recognition but did not require antigen processing. Selective activation was observed for the TCR-Vbeta5 subpopulation. These findings indicate that the I2 protein is a new class of T cell superantigen and suggest that colonization by the I2 microorganism in susceptible hosts may provide a superantigenic stimulus pertinent to Crohns disease pathogenesis.