Yersinia enterocolitica serotype O:3 alters the expression of serologic HLA-B27 epitopes on human monocytes

Abstract

The expression of serologic HLA-B27 epitopes on leukocytes of patients with reactive arthritis or ankylosing spondylitis has been shown to be modified in the course of the disease. The purpose of this work was to study whether phagocytosis of arthritis-triggering microbes in vitro alters the expression of HLA-B27 molecules on human antigen-presenting cells and to characterize the underlying mechanisms. Human monocytes and HLA-B27-or HLA-A2-transfected human U-937 cells were exposed to Yersinia enterocolitica serotype O:3. The expression of different epitopes of HLA-B27 was monitored by using immunofluorescence, and their synthesis was determined by quantitative immunoprecipitation. Our results show that phagocytosis of Y. enterocolitica serotype O:3 changed the expression of serological HLA-B27 epitopes. This was due to the reduced synthesis of HLA-B27 molecules. The expression of especially the epitopes which depend on the presence of peptides in the antigen-binding groove was changed. The expression of the ME1 epitope, which has been shown to be important for T-cell recognition in patients with reactive arthritis, was decreased. Down-regulation of epitopes important for the T-cell recognition may impair the elimination of arthritis-triggering microbes and lead to persistent infection. In addition, Y. enterocolitica serotype O:3 seemed to alter the repertoire of peptides presented by the HLA-B27 molecules on human monocytes. This may have a role in the pathogenesis of reactive arthritis via an autoimmune mechanism.

Invasion bySalmonella typhimuriumInduces Increased Expression of the LMP, MECL, and PA28 Proteasome Genes and Changes in the Peptide Repertoire of HLA-B27

“…A recent study has shown altered expression of serologic HLA-B27 epitopes on human monocytes following exposure to Yersinia or invasion by Salmonella enteritidis, although in contrast with our data, ME1 epitope expression was decreased (33). This could reflect differences in signal transduction and/or antigen processing associated with bacterial invasion.…”

HLA-B27 modulates the survival of Salmonella enteritidis in transfected L cells, possibly by impaired nitric oxide production

“…HLA-B27-and HLA-B7-transfected L cells had stable and comparable cell surface expression of the transfected genes when stained with specific MAbs. Furthermore, the expression level of these transfected genes appeared to be optimal, since it was similar to those of endogenous HLA-B27 and HLA-B7 on human cells (19,34). The expression of human and murine MHC I antigens on the transfectants is shown in Fig.…”

“…As negative controls, isotype-matched mouse MAbs were used. The cells were stained by the indirect immunofluorescence technique by a protocol described earlier (34). Cell surface expression was analyzed by flow cytometry (FACScan; Becton Dickinson, San Jose, Calif.).…”

Alteration of HLA-B27 Peptide Presentation after Infection of Transfected Murine L Cells byShigella flexneri

“…Bacterial products such as lipopolysaccharide may also be detected inside ReA synovial membranes and fluid (9). Various effects of bacterial infection on HLA-B27 biosynthesis and expression have been reported: a decrease in the synthesis of HLA-B27 molecules has been described for Yersinia enterocolitica-infected human monocytes (44), and Salmonella or Yersinia infection may induce alternative splicing of HLA-B27 mRNA, leading to a soluble form of the molecule (12). In our conditions, S. flexneri infection did not affect the expression level of HLA-B27 molecules.…”