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
Laser activated gold pyramids could deliver drugs, DNA into cells without harm
24.03.2017 | Harvard John A. Paulson School of Engineering and Applied Sciences
What does congenital Zika syndrome look like?
24.03.2017 | University of California - San Diego
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
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24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy