2001 Fiscal Year Final Research Report Summary
LFA-I-mediated regulation of immune response by Rapl.
| Project/Area Number |
12670302
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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 |
Immunology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
KATAGIRI Koko KYOTO UNIVERSITY, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (00322157)
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| Co-Investigator(Kenkyū-buntansha) |
KINASHI Tatsuo KYOTO UNIVERSITY, Graduate School of Medicine, Professor, 医学研究科, 教授 (30202039)
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| Project Period (FY) |
2000 – 2001
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| Keywords | LFA-1 / Rap1 / T cell-APC interaction / IL-2 / AICD / Anergy / TCR triggering / Adhesion |
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| Research Abstract |
Activation of T cells by antigen requires adhesive interactions with antigen-presenting cells (APC) in which LFA-1 and ICAMs are important in this process. However, it is not well understood what signaling molecules regulate this process and how modulation of adhesive events influence T cell activation. Here we show that Rap1 is activated in T cells in an antigen-dependent manner and accumulated at the contact site of T cell and antigen-loaded APC. Inhibition of Rap1 activation by a dominant negative Rap1 or SPA-1, a Rap1 GTPase activating protein, abrogates LFA-1/ICAM-1 mediated adhesive interactions with antigen-pulsed APC, and the subsequent TCR triggering and IL-2 production. Conversely, augmented antigen-dependent Rap1 activation by the expression of wild type Rap1 enhances these responses, but culminates in apoptosis by Fas/FasL. Thus, Rap1 functions as a key regulator of T cell and APC interactions and modulates T cell-responses from productive activation to activation-induced cell death by regulating the strength of adhesive interactions. Moreover, constitutive Rap1 activation rendered T cells unresponsive with accumulation of p27^<Kip1>. Our study indicates that the activation state of Rap1 has a decisive effect on the T cell-response to antigen.
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[Publications] Suga, K., Katagiri, K., Kinashi, T., Harazaki, T., Iizuka, T., Hattori, M. and Minato, N.: "CD98 induces LFA-1-mediated cell adhesion in lymphoid cells via activation of Rap1"FEBS letters. 489. 249-253 (2001)
Description
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