ORCID Profile
0000-0002-8544-2689
Current Organisation
京都大学 / Kyoto University
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Publisher: Springer Science and Business Media LLC
Date: 10-02-2008
DOI: 10.1038/NSMB.1382
Abstract: The monoclonal antibody 1A1D-2 has been shown to strongly neutralize dengue virus serotypes 1, 2 and 3, primarily by inhibiting attachment to host cells. A crystal structure of its antigen binding fragment (Fab) complexed with domain III of the viral envelope glycoprotein, E, showed that the epitope would be partially occluded in the known structure of the mature dengue virus. Nevertheless, antibody could bind to the virus at 37 degrees C, suggesting that the virus is in dynamic motion making hidden epitopes briefly available. A cryo-electron microscope image reconstruction of the virus:Fab complex showed large changes in the organization of the E protein that exposed the epitopes on two of the three E molecules in each of the 60 icosahedral asymmetric units of the virus. The changes in the structure of the viral surface are presumably responsible for inhibiting attachment to cells.
Publisher: Springer Science and Business Media LLC
Date: 16-01-2014
DOI: 10.1038/SREP03714
Publisher: The American Association of Immunologists
Date: 15-07-2015
Abstract: Mucosal-associated invariant T (MAIT) cells have a semi-invariant TCR Vα-chain, and their optimal development is dependent upon commensal flora and expression of the nonpolymorphic MHC class I–like molecule MR1. MAIT cells are activated in an MR1-restricted manner by erse strains of bacteria and yeast, suggesting a widely shared Ag. Recently, human and mouse MR1 were found to bind bacterial riboflavin metabolites (ribityllumazine [RL] Ags) capable of activating MAIT cells. In this study, we used MR1/RL tetramers to study MR1 dependency, subset heterogeneity, and protective effector functions important for tuberculosis immunity. Although tetramer+ cells were detected in both MR1+/+ and MR1−/− TCR Vα19i-transgenic (Tg) mice, MR1 expression resulted in significantly increased tetramer+ cells coexpressing TCR Vβ6/8, NK1.1, CD44, and CD69 that displayed more robust in vitro responses to IL-12 plus IL-18 and RL Ag, indicating that MR1 is necessary for the optimal development of the classic murine MAIT cell memory/effector subset. In addition, tetramer+ MAIT cells expressing CD4, CD8, or neither developing in MR1+/+ Vα19i-Tg mice had disparate cytokine profiles in response to RL Ag. Therefore, murine MAIT cells are considerably more heterogeneous than previously thought. Most notably, after mycobacterial pulmonary infection, heterogeneous subsets of tetramer+ Vα19i-Tg MAIT cells expressing CXCR3 and α4β1 were recruited into the lungs and afforded early protection. In addition, Vα19iCα−/−MR+/+ mice were significantly better protected than were Vα19iCα−/−MR1−/−, wild-type, and MR1−/− non-Tg mice. Overall, we demonstrate considerable functional ersity of MAIT cell responses, as well as that MR1-restricted MAIT cells are important for tuberculosis protective immunity.
Publisher: Proceedings of the National Academy of Sciences
Date: 13-07-2020
Abstract: The development of a universal influenza vaccine is a major public health need globally, and identifying the optimal formulation will be an important first step for developing such a vaccine. Here we show that a two-dose immunization of humans with an inactivated, AS03-adjuvanted H5N1 avian influenza virus vaccine engaged both the preexisting memory and naive B cell compartments. Importantly, we show that the recruited memory B cells after first immunization were directed against conserved epitopes within the H5 HA stem region while the responses after the second immunization were mostly directed against strain-specific epitopes within the HA globular head. Taken together these findings have broad implications toward optimizing vaccination strategies for developing more effective vaccines against pandemic viruses.
Publisher: Wiley
Date: 27-08-2009
Location: Japan
No related grants have been discovered for Daved Fremont.