Copolymer 1, also called glatiramer acetate, is an unusual therapeutic compound, a heterogeneous mix of polypeptides containing the four amino acids Y, E, A, and K in definite ratios but with no uniform sequence. Although its mode of action remains controversial, this preparation clearly helps retard the progression of human multiple sclerosis (MS) and of the related autoimmune condition, studied in mice, experimental autoimmune encephalomyelitis (EAE). Copolymer 1 is presented on class II MHC molecules, including the HLA-DR2 type that is associated with increased risk of MS. This MHC molecule binds a defined auto-epitope from myelin basic protein (MBP) and presents it to CD4 T cells, initiating an immune response against myelin in the CNS. Fridkis-Hareli et al. reexamined the structure of the DR2 peptide-binding groove and concluded that the selection of amino acids used in Copolymer 1 was far from optimal if the goal was to compete against presentation of MBP peptides. Here they show that YFAK and FAK copolymers, among others, bind DR2 with higher affinity than does YEAK (copolymer 1), allowing them to compete successfully against an endogenous autoantigenic peptide. These formulations were more effective than Copolymer 1 at suppressing the activation of T cells bearing DR2-restricted, MS patient?derived T cell receptors. Crucially, the novel copolymers were also dramatically more effective at suppressing EAE. Thus, mice injected with either a defined antigenic peptide or whole spinal cord homogenate normally initiate inflammatory and cytolytic responses in the CNS. While Copolymer 1 reduced the incidence of this disease and delayed its onset in most cases, several of the novel copolymers prevented it entirely. Given the precedent of Copolymer 1?s safety and efficacy in people with MS, the use of other copolymers, perhaps optimized to target an individual?s MHC haplotype, seems an attractive scenario for MS and perhaps other autoimmune diseases.
John Ashkenas | EurekAlert
Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital
Highly precise wiring in the Cerebral Cortex
21.09.2017 | Max-Planck-Institut für Hirnforschung
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...
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21.09.2017 | Physics and Astronomy
21.09.2017 | Life Sciences
21.09.2017 | Health and Medicine