1994 Fiscal Year Final Research Report Summary
studies of antigen presentation of peptides by MHC class I molecules
| Project/Area Number |
05454204
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TAKIGUCHI Masafumi Inst.Med.Sci, Univ.Tokyo, Assist.Prof., 医科学研究所, 助手 (00183450)
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| Co-Investigator(Kenkyū-buntansha) |
BECK Yoshifumi Inst.Med.Sci, Univ.Tokyo, Assist.Prof., 医科学研究所, 助手 (70199454)
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| Project Period (FY) |
1993 – 1994
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| Keywords | HLA class I antigens / Antigen presentation / HLA class I binding peptides / TAP antigens / Cytotoxic T cells / Human minor histocompatibility antigens |
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| 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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[Publications] Yoshifumi Beck, Masayuki Sekimata, Setsuko Nakayama, Gerhard A.Muller, Claudia A.Muller, Junji Yamamoto, Takeshi Nagao, Hisanori Uchida, Nobuo Akiyama, Ai Kariyone, and Masafumi Takiguchi: "Expression of human minor histocompatibility antigen on cultured kidney cells." Eur.J.Immunol.23. 467-472 (1993)
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「研究成果報告書概要(欧文)」より
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[Publications] John Sideny, Marie-France del Guercio, Scott Southwood, Victor H.Engelhard, Ettore Appella, Hans-Georg Rammensee, Kristen Falk, Olaf Rotzschke, Masafumi Takiguchi, Ralph T.Kubo, Howard M.Gray and Alessandro Sette: "Several HLA alleles share overlapping peptide specificities." J.Immunol.154. 247-259 (1995)
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「研究成果報告書概要(欧文)」より
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[Publications] Yoshifumi Beck, Leonardo Satz, Yuji Takamiya, Setsuko Nakayama, Lin Ling, Yoshihide Ishikawa, Takeshi Nagao, Hisanori Uchida, Katsushi Tokunaga, Claudia Muller, Takeo Juji and Masafumi Takiguchi: "Polymorphism of human minor histocompatibility antigen : T cellrecognition of human minor histocompatibility peptides presented by HLA-B35 subtype molecules." J.Exp.Med.(in press).
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「研究成果報告書概要(欧文)」より
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