Protein Engineering Potential Inhibitor of Detrimental Immune Responses

On the surface of immune cells, class II major histocompatibility complex proteins (MHCII) present antigenic peptides for CD4+ T cell recognition, which initiate a variety of antigen-specific immune responses such as antibody response or cytotoxic T cell activation. In people with with auto-immune diseases including but not limited to type 1 diabetes, multiple sclerosis, and rheumatoid arthritis, detrimental immune responses occur after the presentation of antigenic peptides. A single-chain, minimal MHCII (scm-MHCII) has been designed to retain its function as an antigen-presenting protein with a simplified structure that can be easily produced and manipulated in a laboratory by recombinant microbial expression. By applying directed evolution and selection for protein stability quantified using yeast surface display (YSD), we have engineered a mutant library which may contain highly stable mutants capable of functioning as a highly specific inhibitor of T cell-mediated immune responses with the potential to be applied to treating a variety auto-immune diseases.