Clonal expansion of CD4(+) TCR beta beta(+) T cells in TCR alpha-chain-deficient mice by gut-derived antigens

A population of CD4(+) alpha(-)beta(+) T cells increases in the mucosal and peripheral lymphoid tissues of TCR alpha-chain-deficient mice with inflamm atory bowel disease. The alpha-beta+ T cells, which produce predominantly I L-4, mediate the proliferation of colonic epithelial crypts and the infiltr ation of large numbers of IgA-producing plasma cells into the lamina propri a of the colon. To examine whether enteric Ags were recognized by a populat ion of monoclonal a-pf T cells leading to the intestinal inflammation, we e xamined the usage and clonotypes of TCR expressed by the alpha(-)beta(+) T cells in TCR alpha-chain-deficient mice with inflammatory bowel disease. An alyses of immunoprecipitates by two dimensional electrophoresis and single- cell RT-PCR revealed that TCR of the alpha(-)beta(+) T cells was a homodime r of beta-chains that was capable of recognizing luminal bacterial Ags. PCR single-strand conformation polymorphism analysis of TCR V beta transcripts revealed monoclonal accumulation of the alpha(-)beta(+) T cells in the col onic lamina propria of the diseased mice. DNA sequencing revealed the accum ulation of the alpha(-)beta(+) T cells with the same CDR3 sequences in the colon. These findings suggest that the pathogenic CD4(+) alpha(-)beta(+) T cells expressing a homodimeric form of the TCR beta-chains can be clonally expanded upon the stimulation with gut-derived Ags.