Grant-in-Aid for Scientific Research (B)
|Allocation Type||Single-year Grants |
|Research Institution||ASAHIKAWA MEDICAL COLLEGE |
KATAGIRI Makoto Asahikawa Medical College, Vice-President, 副学長 (10041823)
KOBAYASHI Hiroya Asahikawa Medical College, School of Medicine, Assistant, 医学部, 助手 (90280867)
SATO Keisuke Asahikawa Medical College, School of Medicine, Assistant Professor, 医学部, 講師 (10250549)
KIMURA Shyoji Asahikawa Medical College, School of Medicine, Professor, 医学部, 教授 (00250548)
AOKI Naoko Asahikawa Medical College, School of Medicine, Assistant, 医学部, 助手 (60301983)
|Project Period (FY)
1997 – 1999
Completed (Fiscal Year 1999)
|Budget Amount *help
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥8,800,000 (Direct Cost: ¥8,800,000)
|Keywords||HLA molecules / HLA-binding peptides / Disease susceptibility / Allele-specific binding motif / 疾患感受性|
The profound polymorphism, one of the unique features of HLA molecules, is linked to (a positive association with) the development of certain diseases. Polymorphic region of HLA molecules interact with the corresponding peptides. The complexes then are presented to and stimulate specific T cells, leading to a variety of consequences. Thus the mode the binding of HLA molecules and peptides may affect the process of the development of HLA linked diseases.
The primary concern of this project has been the identification of specific peptides possibly involved in the pathogenesis of the diseases, examining the interaction of those peptides with HLA molecules and T cells, and subsequently controlling the disease process.
First we have identified the amino acid sequence of the peptides specifically bound to HLA-DR4 and HLA-DR9/DR53, depicting allele specific amino acid sequences (motif). Those two alleles are relatively common in Japanese and are known to have a linkage to certain diseases.
we have investigated peptides which may be involved in the development of such diseases as birch pollinosis, Vogt-Koyanagi-Harada disease and IDDM. We have also examined the possible tumor antigen of malignant melanoma.
Our results are summarized as follows,
1.Birch pollinosis has a positive association with HLA-DR9. A 17kDa protein has been identified to be a major T cell activating antigen. The protein held three HLA-DR9 restricted epitopes and they all bore DR9 specific binding motif. In patients who had no HLA-DR9 their T cells recognized the epitope containing HLA-DQI binding motif.
2.Harada's disease has a positive association with HLA-DR4. T cells from the patient recognized peptides derived from tyrosinase. The peptides bore HLA-DR4 binding motif.
3.I-AィイD1g7ィエD1 has a critical role in the development of insulitis and diabetes in NOD mice, a model of IDDM. Two major peptides from glutamic acid decarboxylase 65(GAD65) have been identified to stimulate T cells from NOD mice. Pretreatment of NOD mice with those peptides prevented the development of insulitis.
4.Tyrosinase was examined for the possible tumor antigen of malignant melanoma. T cells from melanoma patients recognized the peptide derived from tyrcosinase in HLA-DR15 restricted manner.
Our research will present a clue for better understanding a molecular mechanism of disease process and provide the basis for peptide therapy. Less