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
Neutrons produce first direct 3D maps of water during cell membrane fusion
21.09.2018 | DOE/Oak Ridge National Laboratory
Narcolepsy, scientists unmask the culprit of an enigmatic disease
20.09.2018 | Universitätsspital Bern
The building blocks of matter in our universe were formed in the first 10 microseconds of its existence, according to the currently accepted scientific picture. After the Big Bang about 13.7 billion years ago, matter consisted mainly of quarks and gluons, two types of elementary particles whose interactions are governed by quantum chromodynamics (QCD), the theory of strong interaction. In the early universe, these particles moved (nearly) freely in a quark-gluon plasma.
This is a joint press release of University Muenster and Heidelberg as well as the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt.
Then, in a phase transition, they combined and formed hadrons, among them the building blocks of atomic nuclei, protons and neutrons. In the current issue of...
Thin-film solar cells made of crystalline silicon are inexpensive and achieve efficiencies of a good 14 percent. However, they could do even better if their shiny surfaces reflected less light. A team led by Prof. Christiane Becker from the Helmholtz-Zentrum Berlin (HZB) has now patented a sophisticated new solution to this problem.
"It is not enough simply to bring more light into the cell," says Christiane Becker. Such surface structures can even ultimately reduce the efficiency by...
A study in the journal Bulletin of Marine Science describes a new, blood-red species of octocoral found in Panama. The species in the genus Thesea was discovered in the threatened low-light reef environment on Hannibal Bank, 60 kilometers off mainland Pacific Panama, by researchers at the Smithsonian Tropical Research Institute in Panama (STRI) and the Centro de Investigación en Ciencias del Mar y Limnología (CIMAR) at the University of Costa Rica.
Scientists established the new species, Thesea dalioi, by comparing its physical traits, such as branch thickness and the bright red colony color, with the...
Scientists have succeeded in observing the first long-distance transfer of information in a magnetic group of materials known as antiferromagnets.
An international team of researchers has mapped Nemo's genome, providing the research community with an invaluable resource to decode the response of fish to...
21.09.2018 | Event News
03.09.2018 | Event News
27.08.2018 | Event News
21.09.2018 | Physics and Astronomy
21.09.2018 | Life Sciences
21.09.2018 | Event News