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Yersinia enterocolitica serotype O:3 alters the expression of serologic HLA-B27 epitopes on human monocytes
M Wuorela1, S Jalkanen, J Kirveskari
1Department in Turku, National Public Health Institute, University of Turku, Finland. maarit.wuorela@utu.fi
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.
Insights
Phagocytosis of Yersinia bacteria by human cells reduces the synthesis of HLA-B27 molecules, altering T-cell recognition and potentially contributing to reactive arthritis pathogenesis.
Area of Science:
- Immunology
- Molecular Biology
- Pathogenesis of Arthritis
Background:
- Serologic human leukocyte antigen B27 (HLA-B27) epitope expression on leukocytes is altered in reactive arthritis and ankylosing spondylitis.
- The role of microbial phagocytosis in modulating HLA-B27 expression and its implications for disease pathogenesis remain unclear.
Purpose of the Study:
- To investigate if phagocytosis of arthritis-triggering microbes alters HLA-B27 molecule expression on human antigen-presenting cells.
- To characterize the molecular mechanisms underlying these changes in HLA-B27 expression.
Main Methods:
- Human monocytes and U-937 cells (transfected with HLA-B27 or HLA-A2) were exposed to Yersinia enterocolitica serotype O:3.
- Immunofluorescence was used to monitor HLA-B27 epitope expression.
- Quantitative immunoprecipitation assessed HLA-B27 molecule synthesis.
Main Results:
- Phagocytosis of Y. enterocolitica serotype O:3 reduced HLA-B27 molecule synthesis and altered the expression of specific serological epitopes.
- Epitopes dependent on peptide presence in the antigen-binding groove were particularly affected, including the ME1 epitope crucial for T-cell recognition.
- Y. enterocolitica serotype O:3 appeared to alter the peptide repertoire presented by HLA-B27 on human monocytes.
Conclusions:
- Reduced synthesis and altered expression of HLA-B27 epitopes, especially those involved in T-cell recognition, may impair microbial elimination and contribute to persistent infections.
- Changes in the HLA-B27 peptide repertoire may play a role in the autoimmune pathogenesis of reactive arthritis.