A high incidence of Shigella-induced arthritis in a primate species: Major histocompatibility complex class I molecules associated with resistance and susceptiblity, and their relationship to HLA-B27

Julie A. Urvater, Stephen N. McAdam, Jamie H. Loehrke, Todd M. Allen, Jennifer L. Moran, Thomas J. Rowell, Susana Rojo, José A. López De Castro, Joel D. Taurog, David I. Watkins

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

The human major histocompatibility complex (MHC) class I gene, HLA-B27, is a strong risk factor for susceptibility to a group of disorders termed spondyloarthropathies. Rodents that express HLA-B27 develop spondyloarthropathies, implicating HLA-B27 in the etiology of these disorders. To determine whether an HLA-B27-like molecule was associated with spondyloarthropathies in nonhuman primates, we analyzed the MHC class I cDNAs expressed in a cohort of rhesus macaques that developed reactive arthritis after an outbreak of shigellosis. We identified several cDNAs with only limited sequence similarity to HLA-B27. Interestingly, one of these MHC molecules had a B pocket identical to that of HLA-B39. Pool sequencing of radiolabeled peptides bound by this molecule demonstrated that, like HLA-B27 and HLA-B39, it could bind peptides with arginine at the second position. However, extensive analysis of the MHC class I molecules in this cohort revealed no statistically significant association between any particular MHC class I allele and susceptibility to reactive arthritis. Furthermore, none of the rhesus MHC class I molecules bore a strong resemblance to HLA-B27, indicating that reactive arthritis can develop in this animal model in the absence of an HLA-B27-like molecule. Surprisingly, there was a statistically significant association between the rhesus macaque MHC locus allele, Mamu-A*12, and the absence of reactive arthritis following Shigella infection.

Original languageEnglish (US)
Pages (from-to)314-325
Number of pages12
JournalImmunogenetics
Volume51
Issue number4-5
DOIs
StatePublished - 2000

Keywords

  • Autoimmunity
  • Major histocompatibility locus
  • Nonhuman primate
  • Reactive arthritis
  • Spondyloarthropathy

ASJC Scopus subject areas

  • Immunology
  • Genetics

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