1996 Fiscal Year Final Research Report Summary
Search for human islet-derived peptides presented by MHC molecules
| Project/Area Number |
07807098
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内分泌・代謝学
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| Research Institution | Okinaka Memorial Institute for Medical Research |
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Principal Investigator |
NAKANISHI Koji Okinaka Memorial Institute for Medical Research Research associate, 研究員 (80211423)
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| Project Period (FY) |
1995 – 1996
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| Keywords | diabetes mellitus / complex / Antigenic peptide / SOLUBLE HLA / Pancreatic islet |
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| Research Abstract |
Insulin-dependent diabetes mellitus (IDDM) is caused by T-cell mediated autoimmunity. In this process, the presentation of the antigenic peptide by MHC molecule to the T-cell receptor is important. The aim of this study is to identify islet-derived peptide which is presented by MHC class II molecule. The B-cells from IDDM patients were EB transformed and cultured with or without the debris of human neonatal islet cell line. Cell surface proteins were isolated by the detergent and HLA-DR and-DQ moleculse were obtanied by the affinity chromatography. The antigenic peptide, which were eluted by trifluoroacetic acid, were analyzed by the HPLC.Three specific peaks were observed in HLA-DR-associated peptides when B-cells were cultured with the debris of human neonatal islet cell line. We are now sequencing these three peptides.
Besides B lymphocytes, we searched another source of HLA molecules. Soluble form of HLA exisis in the serum. We measured the soluble HLA class I (sHLA) by sandwich ELISA in 40 IDDM patients. At the onset of IDDM,sHLA in patients were lower than normal controls. Its level and dynamics were deferent between the patients with and withou HLA-A24. In IDDM patients with HLA-A2 were low fro 2 years from the onset and, thereafter, they recovered. On the other hand, sHLA continued to decrease until 4 years after the onset in those without HLA-A24. The early comlete beta-cell loss (within 18 Mo. after the onset) was frequent in those with HLA-A24 (5/13) compared with those without HLA-A24 (1/14). The late complete beta-cell loss (36 Mo. after the onset) was more frequent in those without HLA-A24 (7/14) than those with HLA-A24 (0/13). The decline of sHLA was synchronous with massive beta-cell destruction.
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