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

• Published in: Immunogenetics (New York) Vol. 51; no. 4-5; pp. 314 - 325
• Main Authors: Urvater, J. A., McAdam, S. N., Loehrke, J. H., Allen, T. M., Moran, J. L., Rowell, T. J., Rojo, S., López de Castro, J.A., Taurog, J. D., Watkins, D. I.
• Format: Journal Article
• Language: English
• Published: 04-04-2000
• Subjects: histocompatibility antigen HLA; HLA-B27 gene; Macaca mulatta; Primates; Shigella; spondyloarthropathies
• ISSN: 0093-7711; 1432-1211
• DOI: 10.1007/s002510050625

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 A locus allele, Mamu-A*12, and the absence of reactive arthritis following Shigella infection.