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*
Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, WI 53715;
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190;
Eppimune, San Diego, CA 92121;
University of Wisconsin Histocompatibility Laboratory, Division of Laboratory Medicine, Department of Pathology and Laboratory Medicine, Madison, WI 53792;
¶ Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599;
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Pittsburgh Zoo, Pittsburgh, PA 15206; and
#
Wildlife Health Sciences, Bronx, NY 10460
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 
1 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.
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  P. Gomez, C. Mavian, B. Galocha, N. Garcia-Medel, and J. A. Lopez de Castro Presentation of Cytosolically Stable Peptides by HLA-B27 Is Not Dependent on the Canonic Interactions of N-Terminal Basic Residues in the A Pocket J. Immunol., January 1, 2009; 182(1): 446 - 455. [Abstract] [Full Text] [PDF]
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C. A. Herberts, J. J. Neijssen, J. d. Haan, L. Janssen, J. W. Drijfhout, E. A. Reits, and J. J. Neefjes Cutting Edge: HLA-B27 Acquires Many N-Terminal Dibasic Peptides: Coupling Cytosolic Peptide Stability to Antigen Presentation. J. Immunol., March 1, 2006; 176(5): 2697 - 2701. [Abstract] [Full Text] [PDF]
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 E. Merino, V. Montserrat, A. Paradela, and J. A.L. de Castro Two HLA-B14 Subtypes (B*1402 and B*1403) Differentially Associated with Ankylosing Spondylitis Differ Substantially in Peptide Specificity but Have Limited Peptide and T-cell Epitope Sharing with HLA-B27 J. Biol. Chem., October 28, 2005; 280(43): 35868 - 35880. [Abstract] [Full Text] [PDF]
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J. Sidney, S. Southwood, V. Pasquetto, and A. Sette Simultaneous Prediction of Binding Capacity for Multiple Molecules of the HLA B44 Supertype J. Immunol., December 1, 2003; 171(11): 5964 - 5974. [Abstract] [Full Text] [PDF]
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B. Park, S. Lee, E. Kim, and K. Ahn A Single Polymorphic Residue Within the Peptide-Binding Cleft of MHC Class I Molecules Determines Spectrum of Tapasin Dependence J. Immunol., January 15, 2003; 170(2): 961 - 968. [Abstract] [Full Text] [PDF]
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