Peptide binding α1α2 domain of HLA-B27 contributes to the disease pathogenesis in transgenie mice

Sanjay D. Khare, Sonwoo Lee, Michael J. Bull, Julie Hanson, Harvinder S. Luthra, Gunther J. Hammerling, Chella S. David

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Human spondyloarthropathies are strongly associated with a major histocompatibility complex (MHC) class I allele, HLA-B27. HLA-B27 transgenic mice and rats demonstrate many features of these diseases further confirming the role of HLA-B27 in disease. Yet the exact role of this molecule in disease pathogenesis is not clearly understood. We have previously reported spontaneous arthritis and nail disease in HLA-B27 transgenic mice lacking β2-microglobulin (B27+β2m°). These observations along with binding studies of B27 derived peptides to HLA-B27 molecule itself led to two hypotheses: (i) HLA-B27 derived peptide as a source of autoantigen; and (ii) HLA-B27 functions as an antigen presenting molecule. In this report. We confirm spontaneous disease in transgenic mice expressing a hybrid B27 molecule with α1α2 domain of B27 and α3 domain of mouse H-2K(d). These mice developed spontaneous arthritis and nail disease when transferred from specific pathogen free barrier facility to the conventional area. Other control mice with MHC class I transgene (e.g., HLA-B7, HLA-Cw3, and H2-D(d)) did not develop such disease. In a MHC reassembly assay, binding of similar peptides to both wild type and hybrid B27 molecules was observed. In addition, the hybrid B27 molecule lacks at least one of the 3 proposed peptides from the third hypervariable (HV3) region of HLA-B27. These data strongly suggest that HLA-B27 molecule is an antigen presenting molecule rather than a peptide donor in the disease pathogenesis.

Original languageEnglish (US)
Pages (from-to)116-126
Number of pages11
JournalHuman Immunology
Volume60
Issue number2
DOIs
StatePublished - Feb 1999

Fingerprint

HLA-B27 Antigen
Peptides
Nail Diseases
Major Histocompatibility Complex
Transgenic Mice
Arthritis
HLA-B7 Antigen
Transgenic Rats
Specific Pathogen-Free Organisms
Spondylarthropathies
Antigens
Autoantigens
Transgenes
Alleles

Keywords

  • HLA-B27
  • Reactive arthritis
  • Reiter's disease
  • Spondyloarthropathies
  • Transgenic animal model

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Khare, S. D., Lee, S., Bull, M. J., Hanson, J., Luthra, H. S., Hammerling, G. J., & David, C. S. (1999). Peptide binding α1α2 domain of HLA-B27 contributes to the disease pathogenesis in transgenie mice. Human Immunology, 60(2), 116-126. https://doi.org/10.1016/S0198-8859(98)00104-9

Peptide binding α1α2 domain of HLA-B27 contributes to the disease pathogenesis in transgenie mice. / Khare, Sanjay D.; Lee, Sonwoo; Bull, Michael J.; Hanson, Julie; Luthra, Harvinder S.; Hammerling, Gunther J.; David, Chella S.

In: Human Immunology, Vol. 60, No. 2, 02.1999, p. 116-126.

Research output: Contribution to journalArticle

Khare, SD, Lee, S, Bull, MJ, Hanson, J, Luthra, HS, Hammerling, GJ & David, CS 1999, 'Peptide binding α1α2 domain of HLA-B27 contributes to the disease pathogenesis in transgenie mice', Human Immunology, vol. 60, no. 2, pp. 116-126. https://doi.org/10.1016/S0198-8859(98)00104-9
Khare, Sanjay D. ; Lee, Sonwoo ; Bull, Michael J. ; Hanson, Julie ; Luthra, Harvinder S. ; Hammerling, Gunther J. ; David, Chella S. / Peptide binding α1α2 domain of HLA-B27 contributes to the disease pathogenesis in transgenie mice. In: Human Immunology. 1999 ; Vol. 60, No. 2. pp. 116-126.
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