1998 Fiscal Year Final Research Report Summary
Development of TCR-CDR3 vaccine for multiple sclerosis
| Project/Area Number |
09557058
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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 | 展開研究 |
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| Research Field |
Neurology
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| Research Institution | National Istitute of Nueroscience |
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Principal Investigator |
YAMAMURA Takashi National Institute of Neuroscience Division of Demyelinating Disease and Aging, Section Chief, 神経研究所 疾病研究第6部, 室長 (90231670)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Keikichi National Institute of Neuroscience Division of Demyelinating Disease and Aging,, 神経センター・神経研究所 歙病研究第6部, 室長 (40117148)
TABIRA Takeshi National Institute of Neuroscience Division of Demyelinating Disease and Aging,, 神経センター・神経研究所 疾病研究第6部, 部長 (80112332)
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| Project Period (FY) |
1997 – 1998
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| Keywords | autoimmune disease / EAE / TCR vaccine / TCR vaccination / CDR3 vaccine / homunculus / SSCP / idiotype network |
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| Research Abstract |
Autoimmune encephalitogenic T cells tend to express limited sequence motifs in the CDR3 regions of T cell receptor alpha - and beta -chains (Int. Immunol. 6 : 947, 1994). We have recently reported that a peptide sequence from alpha -chain CDR3 of an encephalitogenic clone 4b. 14a would enhance the severity of experi-mental autoimmune diseases including experimental autoimmune encephalomyelitis (EAE), adjuvant arthritis or autoimmune diabetes, regardless of the antigen/MHC specificities (J.Neurosci. Res. 45 : 706-713, 1996). Here we clarify that the observed augmentation of autoimmune encephalomyelitis is probably mediated by a regulatory T cell clone reactive to the CDR3 peptide. We reached the conclusion by generat-ing T cell hybridomas reactive to the peptide and performing adoptive transfer experiments with CDR3 reactive T cells. Of particular note, the single strand conformation polymorphism (SSCP) analysis for T cell clonorype revealed that CDR3 reactive clone is in vivo expanded and present among the CD25^+T cells in naive SJL/J mice. This implies that a single T cell clone reactive to a TCR CDR3 peptide is in a state of persistent activation and expansion. Thus antigen nonspecific between autopathogenic T cells and the regulatory T cells. The result could lead to the development of a new TCR vaccine. In fact, and altered form of the CDR3 peptide may induce inactivation of the regulatory clone, leading to the down-regulation of EAE.Such a vaccine should be of practical value, since it could be effective for different diseases and manage to treat disease even after occurrence of epitope-spreading. We are now focusing on the identifica-tion of an appropriate ligand for the CDR3 reactive regulatory T cells.
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