Project/Area Number |
07457063
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Experimental pathology
|
Research Institution | Sapporo Medical University |
Principal Investigator |
SATO Noriyuki Sapporo Medical University School of Medicine, Associate Ptofessor, 医学部, 助教授 (50158937)
|
Co-Investigator(Kenkyū-buntansha) |
MATSUURA Akihiro Sapporo Medical University School of Medicine, Associate Ptofessor, 医学部, 助教授 (70157238)
|
Project Period (FY) |
1995 – 1996
|
Project Status |
Completed (Fiscal Year 1996)
|
Budget Amount *help |
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1996: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1995: ¥5,700,000 (Direct Cost: ¥5,700,000)
|
Keywords | 70hsp / TAP / proteasome / antigenic peptide / T cell / cell surface / ストレス蛋白質 / 熱ショック蛋白質 / 70kDa hsp / 抗原プロセシング / m-DSG |
Research Abstract |
We previously reported that the 70kDa heat shock cognate protein-like molecule (hsc70) is expressed on the cell surface along with the neoplastic transformation of rat fibroblast and that this molecule is recognized by CD3^+, CD4^-, CD8^-, NKR-P1^-, and TCR-_<alpha> beta^- T (DNT) killer cells in an MHC class Iunrestricted fashion. We investigated the mechanism of interaction between hsc70 and DNT cells. H-ras oncogene-transformed rat fibrosarcoma W31 cells expressed hsc70 on the cell surface in almost the same density when the cells were growing in a conventional 5%FCS (5%W31) as when the cell growth was inhibited in the cultivation with 1%FCS (1%W31) . However, DNT cells lysed only 5%W31, but not 1%W31. Since these observations suggest that certain peptide Ags of the fast growing W31 cells may play a role in the interacyion between hsc70 and DNT cells, we pushed 1%W31 cells with trifluoroacetic acid (TFA) -extracted fast growing W31 tumor Ags of less than 3000 Da in molecular size. We also pulsed 1%W31 with TFA-extracted Ags from moderate growing W14 tumors and whole fetus tissues. Our data indicated that DNT cells were clearly cytotoxic to 1%W31 pushed only with TFA-extracted Ags from W31 tumors. Anti-rat hsc70 mAb completely blocked this cytotoxicity. In addtion, pronase K treatment of Ags clearly inhibited the cytotoxicity by DNT cells. Taken together, these data suggest that the complex of peptide Ag and hsc70 is involved in the cytotoxic mechanism between hsc70 and DNT cells.
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