| Project/Area Number |
05044177
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
SASAZUKI Takehiko Dept.Genet., Med.Inst.Bioreg., Kyushu Univ., Professor, 生体防御医学研究所, 教授 (50014121)
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| Co-Investigator(Kenkyū-buntansha) |
KAMIKAWAJI Nobuhiro Dept.Genet., Med.Inst.Bioreg., Kyushu Univ., 生体防御医学研究所, 助手 (90224659)
MCMICHAEL Andrew j Molecular Immunology Group Institute kof Molecular Medicine John Radcliffe Hospi, 教授
JONES Sarah 英国, オックスフォード大学, 上級研究員
木村 彰方 九州大学, 生体防御医学研究所, 助教授 (60161551)
白澤 専二 九州大学, 生体防御医学研究所, 助手 (10253535)
MCMICHEAL An オックスフォード大学(英国), 教授
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 1995: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1994: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1993: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | HLA / immune regulation / Hepatitis B vaccine / cedar pollinosis / HLA-A2 / HLA-B27 / HLA-B51 / HLA-B52 / DNAタイピング / トランスジェニックスマウス / 溶連菌M蛋白 / HBs抗原 / トランスジェニックマウス / HLA-A遺伝子 / HLA結合ペプチド / T細胞エピトープ |
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| Research Abstract |
To investigate the molecular mechanism of immune response regulated by HLA,we investigated the T cell epitopes on HBs Ag, Cryptomeria Ag and HLA bound peptides eluted from HLA-A2, subtypes and HLA-B27 subtypes. Two antigenic T cell epitopes of Hepatitis B surface antigen (HBsAg), designated as HBs16-31 and HBs81-99, were identified.HBs16-31 was recognized by five HBsAg specific T cell lines from vaccinees with both high and low antibody titers, whereas HBs81-99 was recognized by two T cell lines derived from vaccinees with high antibody titers, suggesting taht HBs81-99 plays a critical role in anti-HBs antibody production in humans vaccinated with HBsAg. Japanese cedar pollinosis is a type I allergic disease caused by Japanese cedar (Cryptomeria japonica) pollen. The frequency of HLA-DP5 (DPA1^<**>02022 and DPB1^<**>0501) was significantly increased in the patients with Japanese cedar pollinosis. Using CPAg-specific T cell lines, we found that disease-associated HLA-DP5 restricted T ce
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lls specific for CPAg existed in the patients. Furthermore, an immunodominant peptide which induced HLA-DP5 restricted Th2 was identified. These observations suggest that the HLA-DP5 may be at least in part involved in the pathogenesis, by helping the IgE antibody production against CPAg. To investigate how single amino acid substitutions in MHC class I molecules affect differences in peptide repertoires, we cluted and sequenced the naturally processed peptides from three HLA-A2 subtypes (HLA-A^<**>0204, -A^<**>0206 and -A^<**>0207) which differ by a single amino acid residue substitution each with -A^<**>0201 at the floor of the binding groove. Allele-specific peptide-motifs for each HLA-A2 subtype substantially differed from that of -A^<**>0201 in the dominant anchor residues. The relative signal intensities for eighteen self peptides determined by mass spectrometry precisely reflected these peptide-motifs. According to the models, the differences in peptide-motifs could be explained by substituted-residue-driven conformational changes for each MHC-peptide complex. These results demonstrate the fine differences among HLA-A2 subtype self peptide repertoires and contribute to the prediction of antigenic peptides. Less
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