Infectious diseases have historically been the leading cause of death worldwide. While cardiovascular disease has slowly overtaken infectious diseases as the leading cause of death over the last 100 years, infectious diseases continue to have a huge burden on our planet, costing millions of life years and trillions of dollars as evidenced by our most recent COVID-19 pandemic. Viral infections like SARS-CoV-2, can be detected and eliminated through the MHC class I antigen presentation pathway. Identifying which viral targets can be recognized by each person's individual immune system is critical, both for evaluating whether current treatments can work, and for developing future vaccines. In my dissertation, I developed a framework to predict and assess susceptibility to infectious disease via peptide-MHC binding.