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H2-A polymorphism contributes to H2-Eβ-mediated protection in collagen-induced arthritis

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Abstract

Collagen-induced arthritis (CIA) is an animal model of auto-immune inflammatory polyarthritis which has features similar to rheumatoid arthritis (RA). Much like RA, susceptibility to mouse CIA is influenced by the major histocompatibility complex (MHC) and is restricted to theH2 haplotypesq andr. In previous experiments, we have found that the introduction of anH2-Eb d transgene in H2-Aq CIA-susceptible mice was able to protect these mice against disease development. More recently, we have proposed that the polymorphism of the first domain of the Eβ molecule modulates this protection, and that the presentation of a peptide from the third hypervariable region of the Eβ chain by the H2-Aq molecule plays an important role in this mechanism. In the present report, we investigated whether the H2-E-mediated protection is H2-Aq-specific and whether the source of collagen has any influence. While the source of collagen had no effect on the protection, our results showed that the H2-E molecule failed to protect B10.RIII (H2r) mice against CIA. Further, theH2 haplotyper exerted a negative effect on the Eβd-mediated protection in H2-Aq-restricted disease. Our results provide additional proof that self-MHC-derived peptides, such as Eβ peptides, may play an important role in the T-cell repertoire education and/or modulation of the T-cell response in the periphery.

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Author notes

  1. Miguel A. Gonzalez-Gay

    Present address: Section of Rheumatology, Hopital Xeral-Lugo, 27004, Lugo, Spain

Authors and Affiliations

  1. Department of Immunology, Mayo Clinic and Mayo Graduate School of Medicine, 55905, Rochester, MN, USA

    Miguel A. Gonzalez-Gay, Eric Zanelli, Sanjay D. Khare & Chella S. David

  2. Department of Rheumatology, Mayo Clinic and Mayo Graduate School of Medicine, 55905, Rochester, MN, USA

    Harvinder S. Luthra

  3. Research Services, Veteran's Affairs Medical Center, 84132, Salt Lake City, UT, USA

    Marie M. Griffiths

  4. Department of Medicine, Division of Rheumatology, University of Utah, 84132, Salt Lake City, UT, USA

    Marie M. Griffiths

Authors
  1. Miguel A. Gonzalez-Gay
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  2. Eric Zanelli
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  3. Sanjay D. Khare
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  4. Christopher J. Krco
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  6. Harvinder S. Luthra
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  7. Chella S. David
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Additional information

The contributions of M. A. Gonzalez-Gay and E. Zanelli in these studies are equal.

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Gonzalez-Gay, M.A., Zanelli, E., Khare, S.D. et al. H2-A polymorphism contributes to H2-Eβ-mediated protection in collagen-induced arthritis. Immunogenetics 44, 377–384 (1996). https://doi.org/10.1007/BF02602783

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  • DOI: https://doi.org/10.1007/BF02602783

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