An aberrant T cell response to enteric bacteria is important in inflammator
y bowel disease. However, the identity of relevant microbial antigens is un
known. Here, we report the presence of I2, a Crohn's disease-associated mic
robial gene, in the murine intestine. The I2 protein induced a proliferativ
e and IL-10 response by CD4(+) T cells from unimmunized mice. The I2 respon
se was dependent on MHC class I1-mediated recognition but did not require a
ntigen processing. Selective activation was observed for the TCR-V beta5 su
bpopulation. These findings indicate that the I2 protein is a new class of
T cell superantigen and suggest that colonization by the I2 microorganism i
n susceptible hosts may provide a superantigenic stimulus pertinent to Croh
n's disease pathogenesis.