We study the human immune system to address fundamental questions in the context of the immune response to different classes of antigens. Our efforts have resulted in the development of high-throughput cell-based screening methods to analyze the repertoire and functional diversity of effector, memory and regulatory T cells in immunocompetent individuals and in immunodeficient patients. These methods, together with high throughput TCRVB sequencing, which can analyze millions of T cell clonotypes in blood or tissues, single-cell gene expression analysis, and cell engineering are used to get insights as to the mechanisms of T cell differentiation and of immune-mediated protection and pathology.