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 enthesop athies such as ankylosing spondylitis. In C57B1/10 mice, transgenic HL A-B2702 as well as H2 genes have been shown to be relative risk facto rs for ANKENT To investigate the role of major histocompatibility comp lex (MHC) class I expression in disease pathogenesis, ANKENT occurrenc e was compared among beta(2)-microglobulin (beta(2)m) knockout litterm ates with or without transgenes for HLA-B2702 and human beta(2)m. In the knockout phenotype lacking beta(2)m, ANKENT occurrence is signific antly reduced (P = 0.016). In the absence of beta(2)m, B2702 is not d etected on the cell membrane, nor does it increase the risk for ANKENT This means that the previous finding that HLA-B2702 increases suscep tibility to ANKENT in C57B1/10 mice cannot be ascribed to a transgene insertion effect. Rather, in order to increase disease susceptibility, B2702 must be coexpressed with mouse beta(2)m (mo-beta(2)m>. In cont rast, when HLA-B2702 is expressed with beta(2)m of human origin, dise ase susceptibility is not affected. Thus, both H2(b)-derived class I h eterodimers and HLA-B2702/mo-beta(2)m heterodimers contribute to ANKE NT susceptibility.