2004 Fiscal Year Final Research Report Summary
The role of MHC sub-region in autoimmune susceptibility and suppressor CD8 T cells
| Project/Area Number |
15500303
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory animal science
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| Research Institution | JUNTENDO UNIVERSITY |
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Principal Investigator |
ZHANG Danqing JUNTENDO UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 助手 (40296877)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUOKA Shouji JUNTENDO UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 助手 (20286743)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Systemic lupus erthematosus (SLE) / New zealand mice / MNC class II / E molecules / H-2 congenic mice / Intreagenic recombination |
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| Research Abstract |
Systemic lupus erythematosus (SLE) is a multigenic autoimmune disease, and the major histocompatibility complex (MHC) class II polymorphism serves as a key genetic element. In SLE-prone (NZB x NZW) F1 mice, the MHC H-2^<d/z> heterozygosity (H-2^d of NZB and H-2^Z of NZW) has a strong impact on disease; thus, congenic H-2^<d/d> homozygous Fl mice do not develop severe disease. In this study, we used Ea-deficient intra-H-2 recombination to establish A^<d/d>-congenic (NZB x NZW) Fl mice, with or without E molecule expression, and dissected the role of class II A and E molecules. Here we found that A^<d/d> homozygous Fl mice lacking E molecules developed severe SLE similar to that seen in wild-type Fl mice, including lupus nephritis, autoantibody production, and spontaneously occurring T cell activation. Additional evidence revealed that E molecules prevent the disease in a dose-dependent manner; however, the effect is greatly influenced by the haplotype of A molecules, because wild-type H-2^<d/z> Fl mice develop SLE, despite E molecule expression. Studies on the potential of dendritic cells to present a self-antigen chromatin indicated that dendritic cells from wild-type Fl mice induced a greater response of chromatin-specific T cells than did those from A^<d/d> Fl mice, irrespective of the presence or absence of E molecules, suggesting that the self-antigen presentation is mediated by A, but not by E, molecules. Our mouse models are useful for analyzing the molecular mechanisms by which MHC class II regions regulate the process of autoimmune responses.
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Research Products
(9 results)
