1993 Fiscal Year Final Research Report Summary
Structure of and signal transduction through T cell receptor complex
| Project/Area Number |
04454206
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | CHIBA UNIVERSITY |
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Principal Investigator |
SAITO Takashi Chiba University School of Medicine, Professor, 医学部, 教授 (50205655)
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| Co-Investigator(Kenkyū-buntansha) |
OHNO Hiroshi Chiba University School of Medicine, Research Associate, 医学部, 助手 (50233226)
MIYATAKE Shoichiro Chiba University School of Medicine, Research Associate, 医学部, 助手 (30239420)
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| Project Period (FY) |
1992 – 1993
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| Keywords | T cell antigen receptor / CD3 complex / Intracellular signal transduction mechanism / CD3zeta family molecules / TCRbeta dimer expression / Signaling motif / PLCgamma1 / Tyrosine phosphorylation |
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| Research Abstract |
There is structural heterogeneity of the T cell receptor-CD3 complex based on the different composition of TCR dimeers or CD3zeta dimers. In vivo, different T cell subsets on differentiation stages possess such different structures. We have analyzed the relationship between the TCR structure and signal transduction.
(1)An immature thymocyte cell line KKF expresses only TCRbeta but not other TCR chains which is associated with CD3 complex on the cell surface. KKFbeta is not special. Transfection of other TCRbeta induced the cell surface expression of the transfected beta chains. The beta dimer associates very weakly with CD3 chains especially with the zeta chain. Introduction of the TCRalpha chain resulted in the expression of only alphabeta dimer which is associated with CD3 chains as strongly as mature T cells. These suggest that beta dimer-expressing thymocytes may be the precursors of alphabeta T cells.
(2)Signal transduction through different TCR isoforms containing different zeta fa
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mily molecules (zeta, eta, FcRgamma) was compared. Any TCR complexes expressing dimeers of zeta, eta or FcRgamma produced IL-2 upon antigen stimulation. However, FcRgamma+ TCR failed to induce activation induced growth inhibiton, whereas eta+TCR did not respond to Thy-1 stimulation. Thus, signals mediated via defferent zeta family molecules appear to be different.
(3)We generated mutant zeta lacking signal motifs to investigate the function of the motif commonly present in CD3 chains. TCR complex lacking zeta motifs could produce IL-2 upon antigen stimulation but did not respond to Thy-1 stimulation. Patterns of tyrosine phosphorylation also differ between the wild-type and mutant zeta. Therefore, there are two types of signals generated through the TCR-CD3 complex ; one through the common signal motifs, the other through strictly zeta family molecules.
(4)According to the analysis of T cell transfectants expressing PDGF receptors, activation of PLCgamma and the PI pathway is not enough to produce IL-2 and co-operation with signals through tyrosine phosphorylation by TCR will be required. Less
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