Competition for antigenic sites during T cell proliferation: A mathematical interpretation of in vitro data

By fitting different mathematical T cell proliferation functions to in vitr o T cell proliferation data, we? studied T cell competition for stimulatory signals, In our lymphocyte proliferation assays both the antigen (Ag) avai lability and the concentration of T cells were varied. We show that prolife ration functions involving T cell competition describe the data significant ly better than classical proliferation functions without competition, thus providing direct evidence for T cell competition in vitro. Our mathematical approach allowed us to study the nature of T cell competition by comparing different proliferation functions involving (i) direct inhibitory T-T inte ractions, (ii) Ag-specific resource competition, or (iii) resource competit ion for nonspecific factors such as growth factors, and access to the surfa ce of Ag-presenting cells (APCs). We show that resource competition is an e ssential ingredient ofT cell proliferation. To discriminate between Ag-spec ific and nonspecific resource competition, the Ag availability was varied i n two manners. In a first approach,ve varied the concentration of APCs, dis playing equal ligand densities; in a second approach we varied the Ag densi ty on the surface of the APCs, while keeping the APC concentration constant . We found that both resource competition functions described the data equa lly well when the Ag availability was increased by adding APCs. When the AP C concentration was kept constant, the nonspecific resource competition fun ction yielded the best description of the data, Our interpretation is that T cells were competing for "antigenic sites" on the APCs.