| Project/Area Number |
03454198
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | Aichi Cancer Center |
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Principal Investigator |
OBATA Yuichi Aichi Cancer Center, Lab.of Immunology, Section Head, 免疫学部, 室長 (30177290)
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| Co-Investigator(Kenkyū-buntansha) |
TAGUCHI Osamu Aichi Cancer Center, Lab.of Experimental Pathology, Senior Researcher, 病理学・第二部, 主任研究員 (00142167)
TAKAHASHI Toshitada Aichi Cancer Center, Vice Director, 副所長 (00124529)
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| Project Period (FY) |
1991 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1993: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1992: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1991: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Keywords | Mouse TL antigen / MHC class I antigen / Transcription factor / Thymic T cell / Intestinal epithelium / Cytotoxic T cell / gammadelta T cells / Antigen presentation / gammadeltaT細胞リセプター / T細胞 / T細胞レセプター / rel / NF-KB遺伝子群 / 胸腺 |
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| Research Abstract |
Mouse TL antigens belong to a family of the major histocompatibility complex (MHC) class I antigens. However, the expression is distinct from other MHC class I antigens, being restricted to normal thymocytes, epithelial cells of the intestine and T cell lymphomas. The aims of the present study were to elucidate the function of TL as well as the structural basis for TL expression. The study was aimed also to delineate the function and maturation steps involved in the differentiation of gammadelta T cells. The results obtained through the study are summarized as follows.
1. Regulation of TL expression : (1) The tissue-specific promoter of TL genes is present in an 80-bp region of the 5' flanking sequence. (2) The nuclear extract of normal thymocytes contains the factor(s) which bind to a DNA fragment containing the promoter region.
2. The function of TL antigens in thymus : The cytotoxic T cell (CTL) clones against TL antigens were established from atransgenic mouse which expresses TL in t
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he thymus and from a C3H mouse which does not. Two of eight CTL clones from transgenic mouse were gammadelta T cells, while all 15 clones from C3H were alphabeta T cells. Thus, the results suggested that the expression of TL in the thymus leads to the selection of T cells belonging to the gammadelta lineage.
3. The function gammadelta T cells. Two gammadelta T cells clones with cytotoxic activity against TL antigens were established as mentioned above. The gammadelta CTL clones do not require an antigenic presentation by H-2 molecules. This indicated that T cell receptors of these cells recognize TL directly, and implied further the function of TL as an antigenic presenting molecule.
4. TL expression in the intestinal epithelium. TL antigens are expressed in the epithelial cells of the small and large intestines of all mice so far tested, including those which do not TL in the thymus. TL antigens are present on the cell surface and cytoplasm of the epithelial cells of villi. This had led to the hypothesis that the major function of TL is to present antigens to neighboring T cells in the gut. Less
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