CHOP Researchers Develop Universal MHC Molecules that Can be Produced Rapidly at Scale
PHILADELPHIA, June 13, 2023 /PRNewswire/ -- Class I major histocompatibility complex (MHC-I) proteins play an essential role in the immune system of all jawed vertebrates. The MHC-I displays peptide fragments of proteins from within the cell on the cell surface, "presenting" them to the immune system, which is constantly scanning the body for foreign or toxic antigens. When foreign peptides are identified, they trigger a cascade that allows cytotoxic T cells to eliminate intruders. This process has been exploited in the development of both vaccines and immunotherapy, wherein researchers identify fragments of peptides unique to viruses or cancer and then screen for T cells that recognize those targets and initiate an immune response.
- However, the current process of using MHC-I molecules as probes in vaccine and immunotherapy development is laborious.
- MHC-I molecules are extremely unstable, and making just one of these molecules can take a week, making it prohibitive to scan large libraries of peptides in an efficient manner.
- Now, researchers from Children's Hospital of Philadelphia (CHOP) have potentially solved this problem by engineering stable, universal MHC-I molecules that can be produced rapidly at scale, allowing researchers not only to develop vaccines and immunotherapies more quickly but also to identify molecules that can work broadly across the population.
- "Universal open MHC-I molecules for rapid peptide loading and enhanced complex stability across HLA allotypes," Proceedings of the National Academy of Sciences, online June 13, 2023, DOI: 10.1073/pnas.2304055120.