1998 Fiscal Year Final Research Report Summary
Analysis of T Cell Antigen Recognition Mechanisms in Autoimmune Hepatitis Patients and Development of Specific Peptide Vaccine.
| Project/Area Number |
09670530
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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 |
Gastroenterology
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| Research Institution | Shinshu University |
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Principal Investigator |
YOSHIZAWA Kaname Shinshu University School of Medicine, Second Department of Internal Medicine, Assistant Professor, 医学部, 講師 (90220615)
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| Project Period (FY) |
1997 – 1998
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| Keywords | autoimmune hepatitis / T cell receptor / complementarity-determining region 3 / size spectratyping / asialoglycoprotein receptor antigen |
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| Research Abstract |
Despite a large number of T cells infiltrating into the liver of patients with autoimmune hepalitis (AIH), little is known about their roles or target antigens. To investigate the roles of these T cells in the pathogenesis of AIR, l) we have studied the clonality of alphabeta T cell populations. in liver tissue by size spectratyping the complementarity-determining region (CDR)3 size lengths of T cell receptor (TCR) Vbeta-chain transcripts and 2) we have tryed to induce asialoglycoprotein receptor antigen (ASGPR)-specific T cells.
1) T cells infiltrating into the liver.
Analysis of ten patients with AIH, who all had the HLA DR4 haplotype, showed clonal expansion in nine liver. More than two T cell clones expanded in most patients. Although the expression of the TCR Vbeta genes was different among the nine patients, clonal expansion of T cells expressing either TCR Vbeta2, 3, 4, 16 or 22 were observed in two patients or more. TCR Vbeta4 clones expanded in 5 cases. Cloning and sequencing of TCR Vbeta CDR3 from PCR products revealed no whole CDR3-shared clones among different patients. In conclusion, a diverse set of T cell clonotypes first recognize target antigens, then expand and accumulate in the liver of AIR patients. These suggest the heterogeneity of autoantigens and the complexity of AIH immunopathogenesis.
2) ASGPR-specific T cells
Periferal blood lymphocytes (PBL) from AIH, chronic hepatitis (CR)-B and -C, primary biliary cirrhosis patients and healthy control were stimulated by ASGPR.T cells of not only AIH but CH-C patients proliferated but those of others did not. It is likely that ASGPR is one of antigen recognized by T cells of AIH and CR-C patients.
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