11 research outputs found

    Structure of a human autoimmune TCR bound to a myelin basic protein self-peptide and a multiple sclerosis-associated MHC class II molecule

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    Multiple sclerosis is mediated by T-cell responses to central nervous system antigens such as myelin basic protein (MBP). To investigate self-peptide/major histocompatibility complex (MHC) recognition and T-cell receptor (TCR) degeneracy, we determined the crystal structure, at 2.8 Å resolution, of an autoimmune TCR (3A6) bound to an MBP self-peptide and the multiple sclerosis-associated MHC class II molecule, human leukocyte antigen (HLA)-DR2a. The complex reveals that 3A6 primarily recognizes the N-terminal portion of MBP, in contrast with antimicrobial and alloreactive TCRs, which focus on the peptide center. Moreover, this binding mode, which may be frequent among autoimmune TCRs, is compatible with a wide range of orientation angles of TCR to peptide/MHC. The interface is characterized by a scarcity of hydrogen bonds between TCR and peptide, and TCR-induced conformational changes in MBP/HLA-DR2a, which likely explain the low observed affinity. Degeneracy of 3A6, manifested by recognition of superagonist peptides bearing substitutions at nearly all TCR-contacting positions, results from the few specific interactions between 3A6 and MBP, allowing optimization of interface complementarity through variations in the peptide

    Developing Spatial Organizations: A Design Based Research Approach (Part I)

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    Measurement of the spin structure of the deuteron in the DIS region

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    We present a new measurement of the longitudinal spin asymmetry Ad and the spin-dependent structure function g(1)(d) of the deuteron in the range 1 < Q(2) < 100 GeV2 and 0.004 < x < 0.7. The data were obtained by the COMPASS experiment at CERN using a 160 GeV polarised muon beam and a large polarised (LiD)-Li-6 target. The results are in agreement with those from previous experiments and improve considerably the statistical accuracy in the region 0.004 < x < 0.03. (c) 2005 Elsevier B.V. All rights reserved

    A SEARCH FOR POINT SOURCES OF EeV PHOTONS

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    Measurements of air showers made using the hybrid technique developed with the fluorescence and surface detectors of the Pierre Auger Observatory allow a sensitive search for point sources of EeV photons anywhere in the exposed sky. A multivariate analysis reduces the background of hadronic cosmic rays. The search is sensitive to a declination band from -85° to +20°, in an energy range from 1017.3 eV to 1018.5 eV. No photon point source has been detected. An upper limit on the photon flux has been derived for every direction. The mean value of the energy flux limit that results from this, assuming a photon spectral index of -2, is 0.06 eV cm-2 s -1, and no celestial direction exceeds 0.25 eV cm-2 s -1. These upper limits constrain scenarios in which EeV cosmic ray protons are emitted by non-transient sources in the Galax
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