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Class I Major Histocompatibility Complex (MHC-I) plays a key role in the antigen processing and presentation pathway crucial for adaptive immunity. There are more than 35,000 human MHC-I alleles, called Human Leukocyte Antigen (HLA). The study and application of this protein has been limited by the instability of its peptide antigen receptive form and its high polymorphism in humans. In previous work (Sun et al, PNAS, 2023), we have addressed these limitations by engineering a disulfide bridge between conserved regions of the heavy and light chain subunits of the complex. Through this, we produce stable and peptide-receptive molecules termed "open MHC-I." Here, we are expanding our approach to the clinically relevant HLA-A*11:01 and HLA-C*07:02 allotypes. We have biophysically confirmed the enhanced thermostability of resulting open MHC-I peptide complexes, relative to wild-type MHC-I, through differential scanning fluorimetry. Further, we show that our open MHC-I molecules are peptide-receptive using fluorescence polarization anisotropy. Our study extends applications of open HLA proteins for diagnosis, vaccine, and therapeutics development. This research is supported by the University of Pennsylvania (Penn) Post-baccalaureate Research and Education Program (PennPREP) funded by the National Institutes of Health (NIH) grant 2R25GM071745-14A1.
Onwuka et al. (Fri,) studied this question.