碩士 / 國立中正大學 / 分子生物研究所 / 101 / Ankylosing spondylitis (AS) is a chronic and progressive inflammatory rheumatic disease that affects the axial skeleton, causing characteristic inflammatory back pain and structural and functional impairments. There is a strong correlation between the expression of Human leukocyte antigen B27 (HLA-B27) subtypes and occurrence of this disease. 90~95% of patients with ankylosing spondylitis carry specific HLA-B27 alleles. As a member of the MHC Class I molecules, the function of HLA-B27 is to present antigens to the immune system. However, how expression of specific HLA-B27 subtype induces inflammation is not entirely clear. There have been increasing interests in the critical role of protein misfolding and unfolded protein response (UPR) of the HLA-B27 heavy chain in modulation of the inflammatory response and progression of AS. In this study, we intend to identify the fundamental difference between AS associated and AS non-associated HLA-B27 molecules. In the rabbit synoviocyte cell line HIG82, AS associated HLA-B2704 protein appears to be trapped inside the endoplasmic reticulum (ER) and that co-expression of β2-microglobulin facilitates its export to the plasma membrane, suggesting a deficiency in the assembly process of the antigen-presenting complex. Addition of the arthritic peptides to HIG-82 showed little effect in assisting the export of HLA-B2704. Furthermore, spliced XBP-1 mRNA is present in HLA-B27 expressing HIG-82, indicating that UPR is activated. On the other hand, although glycosylation status appears to be similar for both AS associated and AS non-associated HLA-B27 molecules, AS associated HLA-B2704 is not presented to the plasma membrane, giving rise to the possibility that AS associated HLA-B27 is targeted to incorrect location inside the cells. Thus, our data indicates that the AS associated HLA-B27 molecules is possibly transported to incorrect target membrane structures, suggesting a potentially putative disease-causing molecular mechanism.
| Identifer | oai:union.ndltd.org:TW/101CCU00061007 |
| Date | January 2013 |
| Creators | Yi-Fang Teng, 鄧怡芳 |
| Contributors | Chin Li, 李沁 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 67 |
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