Thymic Selection and Peripheral Activation of CD8 T Cells by the Same Class I MHC/Peptide Complex

Abstract

Thymic selection is controlled by the interaction between TCR and MHC/peptide. Strength and quality of the signal determine whether thymocytes are selected or deleted. The factors that contribute to this signal remain poorly defined. Here we show that fetal thymic organ cultures (FTOCs) derived from OT-I transgenic mice (the OT-I TCR is restricted by Kb-SIINFEKL) on a KbDb−/− background support positive selection, but only when provided with soluble H-2Kb-SIINFEKL complexes. Selection of CD8 T cells is independent of the valency of the ligand or its capability to coengage CD8 molecules. Both CD8αα and CD8αβ T cells are selected by H-2Kb-SIINFEKL, but only CD8αβ cells are capable of releasing IFN-γ in response to the same ligand. The α4β7 integrin is up-regulated on postselection thymocytes from FTOCs. After adoptive transfer, FTOC-derived OT-I CD8 T cells divide in response to the agonist peptide SIINFEKL. These results establish that CD8 T cells responsive to their nominal peptide-Ag can be generated in FTOC supplemented with soluble MHC class I molecules equipped with the same peptide.