We study the human system to address fundamental questions in the context of the immune response to different classes of antigens, such as microbial pathogens, allergens or self-antigens, to gain insights into mechanisms that induce host protection or immune-mediated pathology. Our efforts towards human immunology have resulted in the development of high-throughput cell-based screening methods to analyze the human immune response and, in particular, the functional diversity and repertoire of human effector and memory T cells. The T cell library method allows the efficient and high-throughput interrogation of the human T cell repertoire without being limited by the complexity of the antigen, the HLA haplotype and the sample size. The method can be used to predict antigenicity and identify T cell epitopes to guide design of T cell vaccines or optimization of biologicals. When applied to the study of T cells in cancer and autoimmunity, it can provide tools for immunotherapy and insights as to the mechanisms of immune-mediated pathology. The T cell library method, together with high throughput TCR Vβ sequencing, which can analyze millions of T cell clonotypes in blood or tissues, mass spectrometry, and single-cell gene expression analysis, can provide a wealth of information that is expected to contribute to the progress in medical immunology research.