| Project/Area Number |
06454219
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Fukui Medical School |
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Principal Investigator |
TOMONARI Kyuhei Fukui Medical School, Department of Immunollogy and Parasitology, Professer, 医学部, 教授 (20251986)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAKUKI Kazuya Fukui Medical School, Department of Pathology (2), Professer, 医学部, 教授 (90024629)
ROSENWASSER O.A Fukui Medical School, Department of Immunollogy and Parasitology, Assistant Prof, 医学部, 教務職員 (90262641)
FAIRCHILD S.P Fukui Medical School, Department of Immunollogy and Parasitology, Assistant Prof, 医学部, 助手 (80262640)
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| Project Period (FY) |
1994 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1994: ¥4,500,000 (Direct Cost: ¥4,500,000)
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| Keywords | Viral superantigens / mouse mammary tumor virus / the T cell repertoie / the T cell receptor / V_β / positive selection / negative selection / superantigens / スーパー抗原 / T細胞受容体V_β / マウス乳癌ウイルス |
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| Research Abstract |
1.Identification of Vbeta4- or Vbeta8.2-specific superantigens (SAGs) encoded by endogenous mouse mammary tumor viruses (Mtvs). Many Mtv sag genes have been found to produce SAGs specific for different Vbetas. Until now, no Vbeta4- or Vbeta8.2-specific SAGs have been identified. We have identified Mtv-encoded SAGs with these specificities in wild-derived spretus mice. We successfully identified the chromosomal locations and nucleotide sequences of these sags. As these mice carry at least 11 Mtvs, thirdor fourth generations of backcross mice with Mtv-free Czech II mice were generated to segregate out these sags. Two sags encoding Vbeta4-specific SAGs were identified and their nucleotide sequences were found to be dissimilar : onehad a sequence similar to sags encoding Vbeta3-specific SAGs, and the other showed no similarity to any sag so far discovered. Using primers specific for various microsatellites these sags were mapped to chromosomes 1 and 6. We also identified two sags encoding
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Vbeta8.2-specific SAGs in these mice. One of these has been shown to have a unique sequence not shared by any other sag.
2.Production of soluble SAGs and their effect on the immune system. The SAG encoded by Mtv7 is so powerful that it induces negative selection, anergy, and proliferation of T cells. To exploit these immune responses to this particular SAG,we produced several types of recombinant soluble fusion proteins. We engineered and cloned a variety of constructs : IgG Fc-SAG7 and the invariant chain-SAG7. However, of these, only the invariant chain-SAG7 constructs had an effect (albeit weak) on both in vivo and in vitro immune responses. Our data indicated that this weak effect was due to weak binding to MHC class II molecules. To overcome this, production of recombinant fusion proteins with soluble CD4 is in progress, as we found CD4 deficient mice which secrete a soluble and functional CD4.
3.Production of antibodies specific for Valpha or Vbeta. As SAGs are specific for Vbetas, it is essential to establish monoclonal antibodies specific for Vbetas. During this research period we have established monoclonals specific for Vbeta8.2/8.3, Vbeta8.3, and Vbeta10a. Less
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