Human leukocyte antigen-DRB1*1502 (DR2Dw 12) transgene reduces incidence and severity of arthritis in mice

Miguel A. Gonzalez-Gay, Eric Zanelli, Sanjay D. Khare, Christopher J. Krco, Paul Zhou, Hidetoshi Inoko, Marie M. Griffiths, Harvinder S. Luthra, Chella S. David

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Abstract

A strong correlation exists between susceptibility to RA in humans and some DRB1 * alleles of the MHC region such as DRB1* 0.401 and DRB1 *0101. Meanwhile, incidences of other specificities, such as DR2* DR5, or DR7 have been found reduced among RA patients. Like RA, susceptibility to mouse CIA is influenced by the MHC class II loci. To analyze the effect of a DRB1 molecule associated with low incidence of RA on mouse CIA, a human DRB1*1502 (DR2Dw12) transgene was introduced inter CIA-susceptible B10.RQB3 (H2A+1) mice. Transgene-positive DHRB1*1502 mice showed a significant reduction in the incidence and severity of arthritis. Moreover, the clinical reduction of arthritis correlated with the T-cell proliferative response of B10.RQB3- DRB1*1502 mice against a self-derived DRBI peptide from the third hypervariable region. Our results suggest that the DRB1 *1502-mediated protection against CIA can be explained by the DRBI molecule acting as a source of self-antigenic peptide which interferes with the T-cull response against immunodominant region(s) of the arthritogenic type II collagen molecule. By analogy, a similar mechanism might play a critical role in influencing the class II-associated predisposition to RA.

Original languageEnglish (US)
Pages (from-to)54-60
Number of pages7
JournalHuman Immunology
Volume50
Issue number1
DOIs
StatePublished - Sep 15 1996

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Gonzalez-Gay, M. A., Zanelli, E., Khare, S. D., Krco, C. J., Zhou, P., Inoko, H., Griffiths, M. M., Luthra, H. S., & David, C. S. (1996). Human leukocyte antigen-DRB1*1502 (DR2Dw 12) transgene reduces incidence and severity of arthritis in mice. Human Immunology, 50(1), 54-60. https://doi.org/10.1016/0198-8859(96)00123-1