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HLA-B27 transgenic rats and strains of HLA-B27-transgenic beta(2)-microglobulin (beta(2)m)-deficient mice develop a multisystem inflammatory disease affecting the joints, skin, and bowel with strong similarity to human spondyloarthritis. We show that HLA-B27 transgenic mice and rats express HC10-reactive, beta(2)m-free HLA-B27 homodimers (B27(2)) and multimers, both intracellularly and at the cell surface of leukocytes, including rat dendritic cells. Fluorescent-labeled tetrameric complexes of HLA-B27 homodimers (B27(2) tetramers) bind to populations of lymphocytes, monocytes, and dendritic cells. The murine (and probably rat) paired Ig-like receptors (PIRs) are ligands for B27(2). Thus, B27(2) tetramers stain RBL cells transfected with murine activating PIR-A4 and inhibitory PIR-B receptors. Murine PIR-A and -B can be immunoprecipitated from the RAW264.7 macrophage cell line, and murine PIR-A can be immunoprecipitated from the J774.A1 line using B27(2). B27(2) tetramer staining corresponds to the distribution of PIR expression on lymphoid and myeloid cells and on murine macrophage cell lines. B27(2) can induce TNF-alpha release from the J774.A1 macrophage cell line. The binding of B27(2) to PIR is inhibited by HC10, an mAb that ameliorates arthritis in HLA-B27(+) beta(2)m(-/-) mice. The expression and PIR recognition of B27(2) could explain the pathogenesis of rodent spondyloarthritis.

Original publication

DOI

10.4049/jimmunol.173.3.1699

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

08/2004

Volume

173

Pages

1699 - 1710

Addresses

Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, United Kingdom.

Keywords

Dendritic Cells, Lymphocyte Subsets, Cell Line, Macrophages, Animals, Animals, Genetically Modified, Mice, Transgenic, Mice, Knockout, Mice, Rats, Spondylarthritis, Spondylitis, Ankylosing, Disease Models, Animal, Biopolymers, Tumor Necrosis Factor-alpha, beta 2-Microglobulin, Receptors, Immunologic, Recombinant Fusion Proteins, Antibodies, Monoclonal, HLA-B27 Antigen, Ligands, Precipitin Tests, Transfection, Biotinylation, Protein Binding, Dimerization