1997 Fiscal Year Final Research Report Summary
Development of killer T cell vaccine against HCV env HVRI
| Project/Area Number |
08670347
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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 |
Virology
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| Research Institution | Yamaguchi University |
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Principal Investigator |
SHIRAI Mutsunori Associate Professor Yamaguchi University School of Medicine, 医学部, 助教授 (20196596)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Hepatitis C / T cell / peptide / MHC / Antibody / Vaccine / HCV / Virus |
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| Research Abstract |
Hypervariable region-1 (HVR1) from the hepatitis C virus (HCV) envelope protein is thought to be a target for neutralizing antibodies. To explore HVR1 recogntion by helper T cells, and their role in antibody responses, we attempted to generate helper T cells specific for HVR1 in mice of three MHC types, and with PBMC from HCV-infected HLA-diverse humans. In both species, HVR1 was presented by >1 class II MHC molecule to CD4^+ helper T cells and showed surprising interisolate crossreactivity. The epitope for two DR4^+ patients was mapped to a more conserved C-terminal sequence containing a DR4 binding motif, possibly accounting for crossreactivity. Strikingly, antibodies to patients' own HVR1 sequences were found only in patients with T cell responses to HVR1, even though all had antibodies to envelope protein, suggesting that induction of antibodies to HVR1 depends on helper T cells specific for a sequence proximal to the antibody epitope. Thus, helper T cells specific for HVR1 may be functionally important in inducing neutralizing antibodies to HCV.These results may be the first example of "T-B reciprocity, " in which proximity of a helper T cell epitope determines antibody epitope specificity, in a human disease setting.
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[Publications] Masaki, T., M.Tokuda, M.Ohnishi, S.Watanabe, T.Fujimura, K.Miyamoto, T.Itano, H.Matsui, K.Arima, M.Shirai, T.Maeba, K.Sogawa, R.Konishi, K.Taniguchi, Y.Hatanaka, O.Hatase and M.Nishioka: "Enhanced expression of the protein kinase substrate Annexin I in human hepatocellular carcinoma." Hepatology. 24. 72-81 (1996)
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