T cells are important to the initiation, prevention, and cure of many diseases. For example, various T cells based cancer immunotherapies have been quite effective in treating several types of cancers. However, a significant fraction of patients do not respond. A comprehensive understanding of the complexity of the T cells repertoire in health and diseases not only provide underlying mechanisms but also new therapeutic targets. In the past several years, we have developed several tools to profile the T cell repertoire from T cell receptor diversity to T cell receptor affinity to multi-dimensional profiling of single T cells in high-throughput. In this talk, I will first introduce these tools and then give examples on how we use them to answer some of the fundamental questions in systems immunology, which in turn help us design new approaches in immune engineering.