A role for CD8 in the developmental tuning of antigen recognition and CD3 conformational change

TCR engagement by peptide-MHC class I (pMHC) ligands induces a conformational change (Delta c) in CD3 (CD3 Delta c) that contributes to T cell signaling. We found that when this interaction took place between primary T lineage cells and APCs, the CD8 coreceptor was required to generate CD3 Delta c. Interestingly, neither enhancement of Ag binding strength nor Src kinase signaling explained this coreceptor activity. Furthermore, Ag-induced CD3 Delta c was developmentally attenuated by the increase in sialylation that accompanies T cell maturation and limits CD8 activity. Thus, both weak and strong ligands induced CD3 Delta c in preselection thymocytes, but only strong ligands were effective in mature T cells. We propose that CD8 participation in the TCR/pMHC interaction can physically regulate CD3 Delta c induction by "translating" productive Ag encounter from the TCR to the CD3 complex. This suggests one mechanism by which the developmentally regulated variation in CD8 sialylation may contribute to the developmental tuning of T cell sensitivity.