The role of MHC class I heterodimer expression in mouse ankylosing enthesopathy

Ankylosing enthesopathy (ANKENT) is a spontaneous mouse joint disease with strikingly similar pathology to human HLA-B27-associated enthesopathies such as ankylosing spondylitis. In C57B1/10 mice, transgenic HLA-B*2702 as well as H2 genes have been shown to be relative risk factors for ANKENT To investigate the role of major histocompatibility complex (MHC) class I expression in disease pathogenesis, ANKENT occurrence was compared among beta(2)-microglobulin (beta(2)m) knockout littermates with or without transgenes for HLA-B*2702 and human beta(2)m. In the knockout phenotype lacking beta(2)m, ANKENT occurrence is significantly reduced (P = 0.016). In the absence of beta(2)m, B*2702 is not detected on the cell membrane, nor does it increase the risk for ANKENT This means that the previous finding that HLA-B*2702 increases susceptibility to ANKENT in C57B1/10 mice cannot be ascribed to a transgene insertion effect. Rather, in order to increase disease susceptibility, B*2702 must be coexpressed with mouse beta(2)m (mo-beta(2)m>. In contrast, when HLA-B*2702 is expressed with beta(2)m of human origin, disease susceptibility is not affected. Thus, both H2(b)-derived class I heterodimers and HLA-B*2702/mo-beta(2)m heterodimers contribute to ANKENT susceptibility.