TY - JOUR
T1 - Human leukocyte antigen-DRB1*1502 (DR2Dw 12) transgene reduces incidence and severity of arthritis in mice
AU - Gonzalez-Gay, Miguel A.
AU - Zanelli, Eric
AU - Khare, Sanjay D.
AU - Krco, Christopher J.
AU - Zhou, Paul
AU - Inoko, Hidetoshi
AU - Griffiths, Marie M.
AU - Luthra, Harvinder S.
AU - David, Chella S.
N1 - Funding Information:
The research of Dr. M. A. Gonzalez-Gay was supported by a fellowship from “Fond0 de Investigaciones Superiores” 94/ 5472 (Spain). Dr. E. Zanelli is supported by NIH Training Grant CA 09127. These studies were supported by NIH Grants AR 30752, AI 14764, and AI 25150, and the Arthritis Foundation. Dr. M. M. Griffiths is supported by Veteran’s Affairs Research funds. The authors thank Suresh Savarirayan for producing the transgenic mice, Michelle K. Smart for the screenings and typings, and Julie Hanson and her crew for breeding and husbandry.
PY - 1996/9/15
Y1 - 1996/9/15
N2 - 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.
AB - 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.
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U2 - 10.1016/0198-8859(96)00123-1
DO - 10.1016/0198-8859(96)00123-1
M3 - Article
C2 - 8872175
AN - SCOPUS:0030587504
VL - 50
SP - 54
EP - 60
JO - Human Immunology
JF - Human Immunology
SN - 0198-8859
IS - 1
ER -