abstract

​Autoimmunity is intrinsically driven by memory T and B cell clones inappropriately targeted at self-antigens. Selective depletion or suppression of self-reactive T cells remains a holy grail of autoimmune therapy, but disease-associated T cell receptors (TCRs) and cognate antigenic epitopes remained elusive. A TRBV9-containing CD8+ TCR motif was recently associated with the pathogenesis of ankylosing spondylitis, psoriatic arthritis and acute anterior uveitis, and cognate HLA-B*27-presented epitopes were identified. Following successful testing in nonhuman primate models, here we report human TRBV9+ T cell elimination in ankylosing spondylitis. The patient achieved remission within 3 months and ceased anti-TNF therapy after 5 years of continuous use. Complete remission has now persisted for 4 years, with three doses of anti-TRBV9 administered per year. We also observed a profound improvement in spinal mobility metrics and the Bath Ankylosing Spondylitis Metrology Index (Bmore...

Protein-protein interactions play key roles in living systems: cell signaling, immune system reactions, microelements transport and many other processes are based on protein-protein complexes functions. Thus, protein-protein complexes prediction is very important task especially in terms of drug discovery. For example, in silico optimization stages of antibody-based drug development process requires to solve the problem hundreds of times. To perform in silico optimization accurately the docking problem must be solved with high accuracy in short time ranges. But it is one of the hardest structural bioinformatics problems due to large solution space (possible molecules orientations), relatively big sizes of protein systems and infinite space of molecules conformations.