Precursors of Functional MHC Class I- or Class II-Restricted CD8αα+ T Cells Are Positively Selected in the Thymus by Agonist Self-Peptides

AbstractThe origin and specificity of αβ TCR+ T cells that express CD8αα have been controversial issues. Here we provide direct evidence that precursors of functional CD8αα T cells are positively selected in the thymus in the presence of agonist self-peptides. Like conventional positive selection, this agonist selection process requires functional TCR α-CPM, whereas it is independent of CD8β expression. Furthermore, CD8αα expression on mature, agonist-selected T cells does not imply selection by MHC class I, and CD8αα+ T cells can be either class I or class II restricted. Our data define a distinct agonist-dependent, positive selection process in the thymus, and they suggest a function for CD8αα distinct from the conventional TCR coreceptor function of CD8αβ or CD4