1995 Fiscal Year Final Research Report Summary
Molecular mechanism of immune response requlated by HLA
| 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
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| Project Period (FY) |
1993 – 1995
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| Keywords | HLA / immune regulation / Hepatitis B vaccine / cedar pollinosis / HLA-A2 / HLA-B27 |
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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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