| Budget Amount *help |
¥17,150,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥2,550,000)
Fiscal Year 2007: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Fiscal Year 2006: ¥6,100,000 (Direct Cost: ¥6,100,000)
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| Research Abstract |
Staphylococcal enterotoxin A (SEA) is an extracellular protein produced by Staphylococcus aureus. SEA shows emetic activity and superantigenic activity. The mechanism of emetic activity of SEA has been little known. In the present study, we demonstrated the following results:
Mutation was carried out at sites of T-cell receptor- and MHC class II molecule-binding regions on SEA by site-directed mutagenesis. We prepared 13 mutant SEA (mSEA) proteins. We examined superantigenic activities of mSEAs in human peripheral blood leukocytes (HPBL) and spleen cells of house musk shrews (Suncus murinus). Moreover, we compared emesis-inducing activities among these mSEAs by intraperitoneal injection. All mSEAs reacted with anti-SEA antibody. Superantigenic activities of mSEAs including N25G, F47G, C96G, C106A, V174G and D227A were deficient because cell proliferation and induction of IL-2, IFN-γ and TNF-α in HPBL were reduced in these mutant proteins. Activities of cell proliferation to spleen cell of house musk shew were reduced in mSEA including F47G, F47S, C96G, C106A, V174G and D227A. Emesis-inducing activities to house musk shew were reduced in F47G, F47S, H61D, H187A and D227A. These results suggest that sites of F47 and D227 on a SEA molecule are essential for both superantigenic and emesis-inducing activities and of H61, H187 and H225 for emesis-inducing activity and that active sites for superantigenic and emesis-inducing activities may be different.
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