Proximity of TCR and its CD8 coreceptor controls sensitivity of T cells

Spatial organisation of T cell receptor (TCR) and its coreceptor CD8 on the surface of live naïve and Ag-experienced CD8+ T cells was resolved by fluorescence lifetime cross-correlation microscopy. We found that exposure of naïve CD8+ T cells to antigen (Ag) causes formation of [TCR, CD8] functional ensembles on the cell surface which correlated with significantly enhanced sensitivity of these cells. In contrast, TCR and CD8 are randomly distributed on the surface of naïve cells. Our model suggests that close proximity of TCR and CD8 can increase Ag sensitivity of T cells by significant accelerating the TCR-peptide-major histocompatibility complex (pMHC) binding rate and stabilisation of this complex. We suggest that the proximity of these primary signalling molecules contributes to the mechanism of functional avidity maturation of CD8+ T cells by switching them from a low to high sensitivity mode.