Homeostatic T Cell Proliferation: How Far Can T Cells Be Activated to Self-Ligands?

Through positive and negative selection, the thymus allows a small fraction of immature CD4⁺8⁺ double positive thymocytes to differentiate into mature CD4⁺8⁻ or CD4⁻8⁺ single positive cells; these cells are released into the periphery to establish the mature T cell pool. Positive selection rescues thymocytes that express TCR with low affinity for peptides bound to MHC molecules expressed on cortical epithelial cells. Conversely, negative selection eliminates thymocytes with high affinity for MHC–peptide complexes, thereby leading to self-tolerance induction 1,2. Via this process of selection, the thymus generates a peripheral repertoire that is largely depleted of overtly autoreactive T cells but retains low but significant reactivity for self-MHC molecules. Retaining weak affinity for self-MHC/peptide ligands has generally been considered a requirement for T cells to optimally recognize foreign...