Human spondyloarthropathies have a strong association with the presence of MHC class I allele, HLA-B27. Spondyloarthropathies occur predominantly in males and are usually triggered by an infection with an enterobacteria. Similar to human disease, experimental animals with HLA-B27 transgene also develop spontaneous inflammatory disease. In addition to HLA-B27, the role of environmental antigens has also been implicated in the animal models. How bacteria interact with HLA-B27 is not yet clearly understood. By breeding HLA-B27 transgenic mice with various transgenic and knock out mice, we investigated the immune mechanism in this inflammatory disease. In this review, we will summarize our recent findings and propose a hypothesis.