Genome-scale T cell activity array and methods of use thereof

A method of making a Genome-Scale T cell Activity Array (GS-TCAA), the method comprising:

• providing a solid support structure comprising a plurality of wells;
• culturing a first cell that expresses a membrane associated anti-CD3 antibody, or antigen-binding fragment thereof, into each of said plurality of wells;
• transfecting said first cell with a cDNA library encoding a plurality of human membrane genes in a manner that allows the display on said first cell of a protein encoded by one of said plurality of human membrane genes;
• and
• co-culturing a second cell that expresses a receptor on the cell surface and a reporter gene into each of said plurality of wells, thereby preparing a Genome-Scale T cell Activity Array,
• wherein interaction between said receptor and said anti-CD3 antibody, or antigen-binding fragment thereof, provides a primary signal and stimulates the activity of said second cell line, and
• wherein an increase in the expression level of said reporter gene indicates that said displayed protein encoded by one of said plurality of human membrane genes acts as a stimulatory co-signaling molecule and stimulates the activity of said second cell line, and wherein a decrease in the expression level of said reporter gene indicates that said displayed protein encoded by one of said plurality of human membrane genes acts as an inhibitory co-signaling molecule and inhibits the activity of said second cell line.