Abstract: In certain embodiments methods of identifying T cell receptors that respond to specific target cell antigens are provided, where the methods comprise providing a substrate bearing a plurality of target cells (e.g., mammalian cells); contacting the target cells on the substrate with CD8+ T cells; and using label-free optical imaging to identify an increase in mass of a T-cell and/or a decrease in mass of a target cell, where an increase in mass of a T cell and/or a decrease in mass of a target cell is an indicator that said T cell bears a T cell receptor activated by antigens presented on said target cell.