Optogenetics often requires genetic modification of the target cells to enable the expression of specific optogenetic tools, making it difficult to study primary cells in their native state. We have recently generated a fully extracellular optogenetic system for reversible light control of T cell receptor (TCR) activation on murine naïve T cells, a cell model that is very difficult to manipulate genetically. This molecular system is very versatile and can be easily modified to study different cell systems in different species. Here we describe how to produce and use this extracellular optogenetic system to manipulate primary T cell activation.