Peptide binding α1α2 domain of HLA-B27 contributes to the disease pathogenesis in transgenic mice
Human spondyloarthropathies are strongly associated with a major histocompatibility complex (MHC) class I allele, HLA-B27. HLA-B27 transgenic mice and rats demonstrate many features of these diseases further confirming the role of HLA-B27 in disease. Yet the exact role of this molecule in disease pa...
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| Hauptverfasser: | , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
1 February 1999
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| In: |
Human immunology
Year: 1999, Jahrgang: 60, Heft: 2, Pages: 116-126 |
| ISSN: | 1879-1166 |
| DOI: | 10.1016/S0198-8859(98)00104-9 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/S0198-8859(98)00104-9 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0198885998001049 
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| Verfasserangaben: | Sanjay D. Khare, Sonwoo Lee, Michael J. Bull, Julie Hanson, Harvinder S. Luthra, Gunther J. Hammerling, and Chella S. David |
| Zusammenfassung: | Human spondyloarthropathies are strongly associated with a major histocompatibility complex (MHC) class I allele, HLA-B27. HLA-B27 transgenic mice and rats demonstrate many features of these diseases further confirming the role of HLA-B27 in disease. Yet the exact role of this molecule in disease pathogenesis is not clearly understood. We have previously reported spontaneous arthritis and nail disease in HLA-B27 transgenic mice lacking β2-microglobulin (B27+β2mo). These observations alongwith binding studies of B27 derived peptides to HLA-B27 molecule itself led to two hypotheses: (i) HLA-B27 derived peptide as a source of autoantigen; and (ii) HLA-B27 functions as an antigen presenting molecule. In this report, we confirm spontaneous disease in transgenic mice expressing a hybrid B27 molecule with α1α2 domain of B27 and α3 domain of mouse H-2Kd. These mice developed spontaneous arthritis and nail disease when transferred from specific pathogen free barrier facility to the conventional area. Other control mice with MHC class I transgene (e.g., HLA-B7, HLA-Cw3, and H2-Dd) did not develop such disease. In a MHC reassembly assay, binding of similar peptides to both wild type and hybrid B27 molecules was observed. In addition, the hybrid B27 molecule lacks at least one of the 3 proposed peptides from the third hypervariable (HV3) region of HLA-B27. These data strongly suggest that HLA-B27 molecule is an antigen presenting molecule rather than a peptide donor in the disease pathogenesis. |
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| Beschreibung: | Falsche Schreibweise von Günter Hämmerling Gesehen am 16.02.2021 |
| Beschreibung: | Online Resource |
| ISSN: | 1879-1166 |
| DOI: | 10.1016/S0198-8859(98)00104-9 |