The specificity of peptides bound to human histocompatibility leukocyte antigen (HLA)-B27 influences the prevalence of arthritis in HLA-B27 transgenic rats

By Ming Zhou, Alain Sayad, William A. Simmons, Richard C. Jones, Shanna D. Maika, Nimman Satumtira, Martha L. Dorris, Simon J. Gaskell, Robert S. Bordoli, R. Balfour Sartor, Clive A. Slaughter, James A Richardson, Robert E Hammer, Joel D Taurog

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45 Scopus citations

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 languageEnglish (US)
Pages (from-to)877-886
Number of pages10
JournalJournal of Experimental Medicine
Volume188
Issue number5
DOIs
StatePublished - Sep 7 1998

Keywords

  • Antigenic peptide
  • Arthritis
  • Human histocompatibility leukocyte antigen B27
  • Mass spectrometry
  • Transgenic rat

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Zhou, B. M., Sayad, A., Simmons, W. A., Jones, R. C., Maika, S. D., Satumtira, N., Dorris, M. L., Gaskell, S. J., Bordoli, R. S., Sartor, R. B., Slaughter, C. A., Richardson, J. A., Hammer, R. E., & Taurog, J. D. (1998). The specificity of peptides bound to human histocompatibility leukocyte antigen (HLA)-B27 influences the prevalence of arthritis in HLA-B27 transgenic rats. Journal of Experimental Medicine, 188(5), 877-886. https://doi.org/10.1084/jem.188.5.877