Abstract
Human histocompatibility leukocyte antigen B27 is highly associated with the rheumatic diseases termed spondyloarthropathies, but the mechanism is not known. B27 transgenic rats develop a spontaneous disease resembling the human spondyloarthropathies that includes arthritis and colitis. To investigate whether this disease requires the binding of specific peptides to B27, we made a minigene construct in which a peptide from influenza nucleoprotein, NP383-391 (SR YWAIR TR), which binds B27 with high affinity, is targeted directly to the ER by the signal peptide of the adenovirus E3/gp19 protein. Rats transgenic for this minigene, NP1, were made and bred with B27 rats. The production of the NP383-391 peptide in B27+NP1+ rats was confirmed immunologically and by mass spectrometry. The NP1 product displaced ~90% of the 3H-Arg-labeled endogenous peptide fraction in B27+NP1+ spleen cells. Male B27+NP1+ rats had a significantly reduced prevalence of arthritis, compared with B27+NPmales or B27+ males with a control construct, NP2, whereas colitis was not significantly affected by the NP1 transgene. These findings support the hypothesis that B27-related arthritis requires binding of a specific peptide or set of peptides to B27, and they demonstrate a method for efficient transgenic targeting of peptides to the ER.
Original language | English (US) |
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Pages (from-to) | 877-886 |
Number of pages | 10 |
Journal | Journal of Experimental Medicine |
Volume | 188 |
Issue number | 5 |
DOIs | |
State | Published - Sep 7 1998 |
Externally published | Yes |
Keywords
- Antigenic peptide
- Arthritis
- Human histocompatibility leukocyte antigen B27
- Mass spectrometry
- Transgenic rat
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology