Provided herein are designs of multi-specific polypeptides for binding target cells and engaging T cells. In some embodiments, the multi-specific polypeptide comprises a first binding domain that specifically binds to a T cell receptor beta variable region (TCRβV), or a T cell receptor alpha variable region (TCRαV) expressed on the T cell, and a second binding domain that specifically binds to an antigen (e.g., CD19) on the target cell, and a Fc region. In some embodiments, both the first and the second binding domains are located on the same polypeptide chain of the Fc region (e.g., a Fc region polypeptide chain comprising a Knob mutation). These multi-specific polypeptides are not only effective in killing the target cells, but also expands early memory populations that maintains and/or replenishes effector populations over time.