1997 Fiscal Year Final Research Report Summary
Prevention of viral infection by helper T cell-epitope vaccine and analysis of its basic mechanism
| Project/Area Number |
08457095
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Mie University |
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Principal Investigator |
KURIBAYASHI Kagemasa Mie University Faculty of Medicine Department of Bioregulation Professor, 医学部, 教授 (10064578)
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| Project Period (FY) |
1996 – 1997
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| Keywords | virus / vaccine / helper T cell / peptide antigen / CTL / Fas / Perforin |
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| Research Abstract |
Effector T cells are generated in syngeneic or semisyngeneic mice after rejection of Friend virus-induced tumor FBL-3. Using FBL-3-specific helper T cell (Th) and cytotoxic T lymphocyte (CTL) clones, we have identified two species of Th epitope (one is I-A^b-binding, the other I-E^b binding) and one CTL epitope which bind to H2D^b. Immunization with the I-E^b binding synthetic peptide effectively prevented susceptible mice from the occurrence of erythroleukemia by Friend virus infection. Effects of I-A^b-binding syhthetic peptide on the prevention was much weaker than that by the I-E^b binding synthetic peptide.
Unexpectedly, most of the Th clones which were established on the basis of their proliferative activities showed peptide-specific cytotoxicity in the context of MHC class II.Alanine substitution of MHC or T cell receptor (TCR) contacting residues in the Th peptides abolished the proliferation of all the Th clones examined. However, the cytotoxic activities of the same Th colnes were little affected by the corresponding mutated peptides. This suggested that recognition of MHC-peptide complexes by Th cells for cytotoxicity is more flexible than that for the stimulation of proliferation. Furthermore, cytolytic machinery used in the Th clones were dependent upon one of the followings : Fas-FasL interaction, perforin-mediated granular exocytosis, and both of the two machineries. These findings might provide a new insight for developing an effective vaccine for viral infection and its prevention.
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