DEGREE OF TCR INTERNALIZATION AND CA2+ FLUX CORRELATES WITH THYMOCYTESELECTION

Recent evidence suggests that TCR down-regulation directly reflects th e number of TCRs that have engaged MHC/peptide ligand complexes. Here, we examined the influence of defined peptides on thymic selection bas ed on their ability to induce differential TCR internalization. Our re sults demonstrate that there is a direct correlation: peptides that in duce strong TCR down-regulation are most efficient at mediating negati ve selection, whereas peptides that induce suboptimal TCR internalizat ion are more efficient at triggering positive selection, As a conseque nce of suboptimal TCR internalization, a proportion of TCR complexes t hat remain on the cell surface may be able to relay continual signals required for survival and differentiation. In addition, we show that t he magnitude of Ca2+ influx set by these peptides reflects the hierarc hy of TCR down-regulation and correlates with positive vs negative sel ection of transgenic thymocytes. Together, our data suggest that T cel l selection is mediated by differing intensities of the same TCR-media ted signal, rather than by distinct signals.