HLA-B27 Heavy Chain Homodimers Are Expressed in HLA-B27 Transgenic Rodent Models of Spondyloarthritis and Are Ligands for Paired Ig-Like Receptors

AbstractHLA-B27 transgenic rats and strains of HLA-B27-transgenic β2-microglobulin (β2m)-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, β2m-free HLA-B27 homodimers (B272) and multimers, both intracellularly and at the cell surface of leukocytes, including rat dendritic cells. Fluorescent-labeled tetrameric complexes of HLA-B27 homodimers (B272 tetramers) bind to populations of lymphocytes, monocytes, and dendritic cells. The murine (and probably rat) paired Ig-like receptors (PIRs) are ligands for B272. Thus, B272 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 B272. B272 tetramer staining corresponds to the distribution of PIR expression on lymphoid and myeloid cells and on murine macrophage cell lines. B272 can induce TNF-α release from the J774.A1 macrophage cell line. The binding of B272 to PIR is inhibited by HC10, an mAb that ameliorates arthritis in HLA-B27+ β2m−/− mice. The expression and PIR recognition of B272 could explain the pathogenesis of rodent spondyloarthritis.