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 C57Bl/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 beta2-microglobulin (beta2m) knockout littermates with or without transgenes for HLA-B*2702 and human beta2m. In the knockout phenotype lacking beta2m, ANKENT occurrence is significantly reduced (P = 0.016). In the absence of beta2m, 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 C57Bl/10 mice cannot be ascribed to a transgene insertion effect. Rather, in order to increase disease susceptibility, B*2702 must be coexpressed with mouse beta2m (mo-beta2m). In contrast, when HLA-B*2702 is expressed with beta2m of human origin, disease susceptibility is not affected. Thus, both H2(b)-derived class I heterodimers and HLA-B*2702/mo-beta2m heterodimers contribute to ANKENT susceptibility.
Weinreich
S S
SS
The Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Department of Transplantation Immunology, Amsterdam.
Hoebe-Hewryk
B
B
van der Horst
A R
AR
Boog
C J
CJ
Ivanyi
P
P
D000818:Animals; D000844:Ankylosis / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D019281:Dimerization; D005838:Genotype; D006183:H-2 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D015796:HLA-B27 Antigen / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D015994:Incidence; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D019076:Transgenes; D001613:beta 2-Microglobulin / Q000235:genetics / Q000627:therapeutic use
D006183:H-2 Antigens; D015796:HLA-B27 Antigen; D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin