A high incidence of Shigella-induced arthritis in a primate species: major histocompatibility complex class I molecules associated with resistance and susceptibility, and their relationship to HLA-B27.
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.
Urvater
J A
JA
Wisconsin Regional Primate Research Center, University of Wisconsin-Madison 53715, USA.
McAdam
S N
SN
Loehrke
J H
JH
Allen
T M
TM
Moran
J L
JL
Rowell
T J
TJ
Rojo
S
S
López de Castro
J A
JA
Taurog
J D
JD
Watkins
D I
DI
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D016918:Arthritis, Reactive / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D015331:Cohort Studies; D004198:Disease Susceptibility; D004405:Dysentery, Bacillary / Q000150:complications*; D005260:Female; D005805:Genes, MHC Class I; D015235:HLA-B Antigens / Q000235:genetics; D015796:HLA-B27 Antigen / Q000235:genetics*; D059946:HLA-B39 Antigen; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D007113:Immunity, Innate; D008253:Macaca mulatta; D008297:Male; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D012763:Shigella flexneri
D015235:HLA-B Antigens; D015796:HLA-B27 Antigen; D059946:HLA-B39 Antigen; D015395:Histocompatibility Antigens Class I