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

• Published in: The Journal of immunology (1950) 1998-01, Vol.160 (1), p.101-106
• Main Authors: Khare, Sanjay D, Bull, Michael J, Hanson, Julie, Luthra, Harvinder S, David, Chella S
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antigen-Presenting Cells - immunology; Arthritis - immunology; beta 2-Microglobulin - deficiency; Female; Histocompatibility Antigens Class II - immunology; HLA-B27 Antigen - immunology; Humans; Immune Tolerance; Inflammation - immunology; Male; Mice; Mice, Transgenic; Molecular Sequence Data; Nail Diseases - immunology; Peptides - chemistry; Peptides - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.160.1.101

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.