1992 Fiscal Year Final Research Report Summary
Role of Antigenic Milieu on the Generation of Autoreactive Immune Repertoire
| Project/Area Number |
03670258
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | National Institute of Neuroscience, NCNP |
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Principal Investigator |
YAMAMOTO Hiroshi Dept. Immunol., Natl. Inst. Neurosci, NCNP Director, 神経研究所・免疫研究部, 部長 (50127312)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEUCHI Tamotsu Dept. Immunol., Natl. Inst. Neurosci, NCNP Staff Scientist, 神経センター・神経研究所・免疫研究部, 研究員 (50226990)
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| Project Period (FY) |
1991 – 1992
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| Keywords | repertoire / idiotype / T cells / thymus / thymic epithelial cells / cell interaction |
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| Research Abstract |
(1). MOPC104E myeloma idiotype (M104E CRI) is immunogenic in inducing CRI-specific T cells. In order to investigate the CRI dependent T cell repertoire selection mechanisms, M104E heavy chain gene transfected B cell lines were establish-ed. Several T cell lines reactive to the CRI were also established from BALB/c mice. One of them exhibited significant and specific proliferative response against M104E gene transfected cell line. Fine specificity analysis using CDR2 peptide (on which the CRI locates) is now underway. Myelin associated glycoprotein (MAG) gene transfected B cell lines were also established. The cell lines may sensitize T cells resulted in the induction of T cell mediated autoimmune neuropathy. The T cell repertoire of the effector cells will be investigated.
(2). Thymic epithelial cell line, SL10.3, was established. The cells supports the proliferation of immature thymocytes and of a certain T cell clone. The novel monoclonal antibody (QR6.6) reactive to the T cell clone was raised. QR6.
6 detects 100kd molecule on immature thymocytes. The molecular analysis of the molecule is in progress. On the other hand, monoclonal antibodies reactive to 45kd or 60kd molecule of thymic epithelial cells were also established. A candidate cDNA fragments for the 60kd molecule were cloned. The DNA sequence analysis revealed that the cDNA is coding for a novel molecule. The cloning of full-length cDNA is now underway.
(3). Transfection of various genes coding for self antigens, such as M104E, MAG, myelin basic protein, and stress proteins, into thymic epithelial cells, and immunize them to mice may sensitize or tolerize T cells. This approach will give us a usuful model system to manipulate the self-specific immunity.
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