Gorillas with spondyloarthropathies express an MHC class I molecule with only limited sequence similarity to HLA-B27 that binds peptides with arginine at P2

J. A. Urvater, H. Hickman, J. L. Dzuris, K. Prilliman, T. M. Allen, K. J. Schwartz, D. Lorentzen, C. Shufflebotham, E. J. Collins, D. L. Neiffer, B. Raphael, W. Hildebrand, A. Sette, David Watkins

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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 α1 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.

Original languageEnglish
Pages (from-to)3334-3344
Number of pages11
JournalJournal of Immunology
Volume166
Issue number5
StatePublished - Mar 1 2001
Externally publishedYes

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Gorilla gorilla
Spondylarthropathies
HLA-B27 Antigen
Arginine
Peptides
Ligands
MHC Class I Genes
Amino Acids
Molecular Models
Primates
Rodentia

ASJC Scopus subject areas

  • Immunology

Cite this

Gorillas with spondyloarthropathies express an MHC class I molecule with only limited sequence similarity to HLA-B27 that binds peptides with arginine at P2. / Urvater, J. A.; Hickman, H.; Dzuris, J. L.; Prilliman, K.; Allen, T. M.; Schwartz, K. J.; Lorentzen, D.; Shufflebotham, C.; Collins, E. J.; Neiffer, D. L.; Raphael, B.; Hildebrand, W.; Sette, A.; Watkins, David.

In: Journal of Immunology, Vol. 166, No. 5, 01.03.2001, p. 3334-3344.

Research output: Contribution to journalArticle

Urvater, JA, Hickman, H, Dzuris, JL, Prilliman, K, Allen, TM, Schwartz, KJ, Lorentzen, D, Shufflebotham, C, Collins, EJ, Neiffer, DL, Raphael, B, Hildebrand, W, Sette, A & Watkins, D 2001, 'Gorillas with spondyloarthropathies express an MHC class I molecule with only limited sequence similarity to HLA-B27 that binds peptides with arginine at P2', Journal of Immunology, vol. 166, no. 5, pp. 3334-3344.
Urvater, J. A. ; Hickman, H. ; Dzuris, J. L. ; Prilliman, K. ; Allen, T. M. ; Schwartz, K. J. ; Lorentzen, D. ; Shufflebotham, C. ; Collins, E. J. ; Neiffer, D. L. ; Raphael, B. ; Hildebrand, W. ; Sette, A. ; Watkins, David. / Gorillas with spondyloarthropathies express an MHC class I molecule with only limited sequence similarity to HLA-B27 that binds peptides with arginine at P2. In: Journal of Immunology. 2001 ; Vol. 166, No. 5. pp. 3334-3344.
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AU - Dzuris, J. L.

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AU - Allen, T. M.

AU - Schwartz, K. J.

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AU - Shufflebotham, C.

AU - Collins, E. J.

AU - Neiffer, D. L.

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