Spontaneous inflammatory disease in HLA-B27 transgenic mice is independent of MHC class II molecules: a direct role for B27 heavy chains and not B27-derived peptides.
Although association of HLA-B27 with human spondyloarthropathies has been known for several years, its role in disease pathogenesis is not understood. Recently, a few investigators have proposed that presentation of B27-derived peptides by MHC class II molecules may be the underlying mechanism. HLA-B27 transgenic rat and mouse models have provided a new tool for understanding the exact role of B27 in disease pathogenesis. HLA-B27 mice lacking endogenous beta2-microglobulin (B27+ beta2m(o)) develop disease after they are transferred from the barrier facility to the conventional colony. This model was utilized to test the hypothesis that B27-derived peptide presented by MHC class II molecules is the cause of the disease. The MHC class II knockout gene, A beta(o), was bred into our B27+ beta2m(o) mice, and disease manifestation was monitored. These mice develop spontaneous disease, demonstrating that MHC class II molecules do not play a major role in B27-related disease. Thus, the disease is not manifested by presentation of B27-derived peptides by class II molecules, since these mice are devoid of H2-A and H2-E molecules. Furthermore, in vivo treatment with mAb against the heavy chain of B27 reduced the incidence of disease in B27+ beta2m(o) mice. Our results clearly demonstrate that B27 heavy chains are directly involved in the disease process.
Khare
S D
SD
Department of Immunology, Mayo Clinic and Medical School, Rochester, MN 55905, USA.
Bull
M J
MJ
Hanson
J
J
Luthra
H S
HS
David
C S
CS
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001168:Arthritis / Q000276:immunology; D005260:Female; D015796:HLA-B27 Antigen / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation / Q000276:immunology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009260:Nail Diseases / Q000276:immunology; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D001613:beta 2-Microglobulin / Q000172:deficiency
D015796:HLA-B27 Antigen; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D001613:beta 2-Microglobulin