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MHC class I molecules and Antigen Presentation

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  • Research in Dolan lab focuses primarily on the adaptive immune system and ways it can be better utilized to eliminate infected or transformed cells. Research focuses on the major histocompatibility (MHC) class I antigen presentation pathway, which plays an important role in alerting the immune system of the presence of intracellular pathogens. When infected, cells notify the immune system of a foreign body by degrading intracellular proteins and presenting the resultant peptides on MHC class I molecules at the cell surface. These peptide-MHC class I complexes are presented on the surface to allow for interaction with the T cell receptors expressed on cytotoxic T lymphocytes. If the T cell recognizes the peptide presented as foreign, they are able to react and kill the cell. In addition to foreign peptides, tumor cells can also present peptides that are tumor-specific and can be recognized by cytotoxic T cells. This process allows cells displaying peptides from infectious or neoplastic agents to be removed by T cells.In order to study antigen presentation, including DRiP presentation the lab has developed a model protein which contains a destabilization domain, followed by an antigenic peptide, and then a fluorescent protein. We can control protein stability by adding a small molecules which interacts with the destabilization domain and allows the protein to fold and function properly. We have so far created two constructs that contain different antigenic peptides which bind to different MHC class I molecules.
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