Gorillas with spondyloarthropathies express an MHC class I molecule with only limited sequence similarity to HLA-B27 that binds peptides with arginine at P2.
The human MHC class I gene, HLA-B27, is a strong risk factor for susceptibility to a group of disorders termed spondyloarthropathies (SpAs). HLA-B27-transgenic rodents develop SpAs, implicating HLA-B27 in the etiology of these disorders. Several nonhuman primates, including gorillas, develop signs of SpAs indistinguishable from clinical signs of humans with SpAs. To determine whether SpAs in gorillas have a similar HLA-B27-related etiology, we analyzed the MHC class I molecules expressed in four affected gorillas. Gogo-B01, isolated from three of the animals, has only limited similarity to HLA-B27 at the end of the alpha1 domain. It differs by several residues in the B pocket, including differences at positions 45 and 67. However, the molecular model of Gogo-B*0101 is consistent with a requirement for positively charged residues at the second amino acid of peptides bound by the MHC class I molecule. Indeed, the peptide binding motif and sequence of individual ligands eluted from Gogo-B*0101 demonstrate that, like HLA-B27, this gorilla MHC class I molecule binds peptides with arginine at the second amino acid position of peptides bound by the MHC class I molecule. Furthermore, live cell binding assays show that Gogo-B*0101 can bind HLA-B27 ligands. Therefore, although most gorillas that develop SpAs express an MHC class I molecule with striking differences to HLA-B27, this molecule binds peptides similar to those bound by HLA-B27.
Urvater
J A
JA
Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, WI 53715, USA.
Hickman
H
H
Dzuris
J L
JL
Prilliman
K
K
Allen
T M
TM
Schwartz
K J
KJ
Lorentzen
D
D
Shufflebotham
C
C
Collins
E J
EJ
Neiffer
D L
DL
Raphael
B
B
Hildebrand
W
W
Sette
A
A
Watkins
D I
DI
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001168:Arthritis / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D020022:Genetic Predisposition to Disease; D006071:Gorilla gorilla; D015796:HLA-B27 Antigen / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D013166:Spondylitis / Q000276:immunology*
D015796:HLA-B27 Antigen; D015395:Histocompatibility Antigens Class I; D009842:Oligopeptides; D001120:Arginine