Project/Area Number |
05454204
|
Research Category |
Grant-in-Aid for General Scientific Research (B)
|
Allocation Type | Single-year Grants |
Research Field |
Immunology
|
Research Institution | The University of Tokyo |
Principal Investigator |
TAKIGUCHI Masafumi Inst.Med.Sci, Univ.Tokyo, Assist.Prof., 医科学研究所, 助手 (00183450)
|
Co-Investigator(Kenkyū-buntansha) |
BECK Yoshifumi Inst.Med.Sci, Univ.Tokyo, Assist.Prof., 医科学研究所, 助手 (70199454)
|
Project Period (FY) |
1993 – 1994
|
Project Status |
Completed (Fiscal Year 1994)
|
Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1994: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1993: ¥4,400,000 (Direct Cost: ¥4,400,000)
|
Keywords | HLA class I antigens / Antigen presentation / HLA class I binding peptides / TAP antigens / Cytotoxic T cells / Human minor histocompatibility antigens / 抗原ペプチド / HLAクラスI分子 / TAP / アロペプチド / マイナー組織適合抗原ペプチド |
Research Abstract |
1.We found that assembly rate of HLA-B35 molecules is faster than that of HLA-B51 molecules. One can speculate that the difference of peptide binding affinity to these HLA class I molecules result in that of assembly rate. To investigate peptide binding to HLA class I molecules, we established novel binding assay using RMA-S cells trasnfected with HLA class I genes. Analysis of binding of peptides carrying anchor residues of HLA-B35 or B51 to these HLA class I molecules indicate that the peptide binding affinity to HLA-B51 is significantly weaker than that to HLA-B35. These findings imply that the difference of assembly rate may result from that of peptide binding to these HLA class I molecules in endoplasmic reticurum. 2.In order to clarify self-peptides recognized by T cells, we attempted to isolate allopeptides recognized by HLA-B51 alloreactive CTL.In HPLC fraction of peptides isolated from purified HLA-B51 molecules, a TAP dependent peptide recognized by one HLA-B51 alloreactive CTL clone was detected. This approach is very useful for studies of antigen presentation and T cell recognition. 3.Polymorphism and antigen presentation of human minor histocompatibility (hmH) antigens were studied using hmH specific CTL clones. The CTL clones killed most target cells expressing HLA-B35, while they failed to kill the cells expressing HLA-B35 subtypes. Since the specific hmH peptides could be isolated form these cells expressing HLA-B35 subytypes, hmH antigens are thought to be conserved among populations.
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