Since lumenal bacteria have been postulated to play an Important role in the pathogenesis of inflammatory bowel disease (IBD), we investigated the humoral response to cecal aerobic bacterial antigens by Western blot analysis in TCRα⁺ mice which spontaneously develop IBD. The sera from TCRα⁺ mice revealed an alteration of the recognition pattern against aerobic bacterial antigens from polyclonal to oligoclonal with age. This alteration was not observed in TCRδ⁺ and TCRα⁺├ mice. The alteration of the recognition pattern in TCRα⁺ mice was associated with production of autoantibodies against tropomyosin and the development of IBD. The unique population of CD4⁺ TCRα⁻β⁺ cells in TCRα⁺ mice may be involved in the recongnition of these bacterial antigens and the absence of the α chain may result in the alteration of immune response.