| Project/Area Number |
14570293
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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 |
Immunology
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| Research Institution | Aichi Cancer Center Research Institute |
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Principal Investigator |
TSUJIMURA Kunio Aichi Cancer Center, Div.Immunology, Head, 腫瘍免疫学部, 室長 (10227407)
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| Co-Investigator(Kenkyū-buntansha) |
OBATA Yuichi RIKEN, BioResource Center, Chief, バイオリソースセンター, 室長 (30177290)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | TL antigen / CTL / Intraepithelial Lymphocyte / MHC tetramer / CD8 |
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| Research Abstract |
Mouse thymus-leukemia antigens (TL) belong to the family of major histocompatibility complex (MHC) class Ib antigens and have a unique manner of expression, i.e., in contrast to other MHC class Ib or Ia antigens, they are found restricted to the intestines in all mouse strains and the thymus of certain examples (TL^+ strains). Although some strains (TL^-strains) do not express TL in the thymus, a proportion of their T lymphomas/leukemias feature TL as a tumor antigen.
TL was originally defined as a serologically defined antigen, and subsequently we have succeeded in generating T cell receptor (TCR)αβ and γδ cytotoxic T lymphocytes (CTL) recognizing TL. We previously reported that the CTL epitope is TAP-independent, but it has not been determined whether an antigenic molecule(s) presented by TL is involved in the recognition of TL-specific CTL. In the present study, we are able to show that TL-specific CTL recognition of TL-specific CTL. In the present study, we are able to show that TL-specific CTL recognize the α1/α2 domain of TL without any additional antigen molecules by use of TL tetramers free from peptides and transfectants expressing various TL/H-2 chimeric molecules. These results suggest that TL plays a specialized role(s) rather than antigen presentation in vivo.
We previously reported that one of TL functions in the thymus is positive selection of TCRγδCTL. In the present study, we showed that TL tetramers can bind to normal intestinal intraepithelial lymphocytes (iIEL) and thymocytes in a CD8-dependent, but TCR/CD3-independent manner, while their binding to TL-specific CTL is well as in the thymus. A recent report by Kronenberg's group showed that the physiological ligand of TL in the intestines is CD8αα homodimer and that TL plays a regulatory role for the activation CD8αα^+ iIELs. The precise mechanisms fro such feedback regulation are now under investigation.
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