| Project/Area Number |
63570228
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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 | Juntendo University School of Medicine |
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Principal Investigator |
YAGITA Hideo Juntendo Univ. Sch. Med., Associate Professor, 医学部, 助教授 (30182306)
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| Co-Investigator(Kenkyū-buntansha) |
OKUMURA Ko Juntendo Univ. Sch. Med., Professor, 医学部, 教授 (50009700)
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1989: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1988: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | CD2 / T cell / B cell / NK cell / Differentiation / Activation / Adhesion molecule / Monoclonal antibody / マウス / cDNA / モノクローナル抗体 / トランスフェクタント / リンパ球機能 / T細胞の分化 / B細胞の分化 |
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| Research Abstract |
1. We cloned and sequenced the murine CD2 cDNA and noted a highly conserved primary structure of its cytoplasmic region between human and mouse CD2.
2. We established five rat anti-mouse CD2 mAbs by screening their reactivities to rat fibroblasts transfected with the mouse CD2 cDNA.
3. By FACS and Northern blot analyses, we revealed that most B cells as well as T and NK cells express CD2 in mice unlike in humans. CD2 appeared on murine B cells at the pre-B stage.
4. We demonstrated the adhesion function of mouse CD2 and inhibitory effects of our mAbs on it.
5. We established additional hamster mabs reactive with distinct epitopes from those recognized by rat mabs by immunizing with affinity-purified mouse CD2 molecules. Certain combinations of the rat and hamster mabs induced mouse T cell activation and proliferation, indicating that mouse CD2 constitutes an alternative pathway of T cell activation like human CD2.
6. A CD2^- T cell hybridoma could respond to 40 to 10-fold lower concentrations of the Ag after CD2 introduction by cDNA transfection. Such an augmentation of Ag response was not observed after introduction of a mutant CD2 lacking most of cytoplasmic region, indicating an importance of the CD2-mediated signal transduction in regulating T cell Ag response.
7. Introduction of CD2 into a CD2^- NK cell line induced binding and cytotoxicity against certain target cells. In contrast, that of cytoplasmic deletion mutant led to a comparable binding but a greatly reduced cytotoxicity, demonstrating an important role of CD2 in regulating NK cell binding and cytotoxicity.
8. CD2 appeared on murine thymocytes very early during fetal thymus ontogeny. However, so far no effect of anti-CD2 mAbs on T cell development has been observed when added into fetal thymus organ cultures.
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