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 language | English (US) |
|---|---|
| Pages (from-to) | 54-60 |
| Number of pages | 7 |
| Journal | Human Immunology |
| Volume | 50 |
| Issue number | 1 |
| DOIs | |
| State | Published - Sep 15 1996 |
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ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
Human leukocyte antigen-DRB1*1502 (DR2Dw 12) transgene reduces incidence and severity of arthritis in mice. / Gonzalez-Gay, Miguel A.; Zanelli, Eric; Khare, Sanjay D.; Krco, Christopher J.; Zhou, Paul; Inoko, Hidetoshi; Griffiths, Marie M.; Luthra, Harvinder S.; David, Chella S.
In: Human Immunology, Vol. 50, No. 1, 15.09.1996, p. 54-60.Research output: Contribution to journal › Article
}
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.
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.
UR - http://www.scopus.com/inward/record.url?scp=0030587504&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030587504&partnerID=8YFLogxK
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 -