Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Recent evidence suggests that TCR down-regulation directly reflects the number of TCRs that have engaged MHC/peptide ligand complexes. Here, we examined the influence of defined peptides on thymic selection based on their ability to induce differential TCR internalization. Our results demonstrate that there is a direct correlation: peptides that induce strong TCR down-regulation are most efficient at mediating negative selection, whereas peptides that induce suboptimal TCR internalization are more efficient at triggering positive selection. As a consequence of suboptimal TCR internalization, a proportion of TCR complexes that remain on the cell surface may be able to relay continual signals required for survival and differentiation. In addition, we show that the magnitude of Ca2+ influx set by these peptides reflects the hierarchy of TCR down-regulation and correlates with positive vs negative selection of transgenic thymocytes. Together, our data suggest that T cell selection is mediated by differing intensities of the same TCR-mediated signal, rather than by distinct signals.


Journal article


Journal of immunology (Baltimore, Md. : 1950)

Publication Date





6030 - 6037


Department of Medical Biophysics and Immunology, Ontario Cancer Institute, Canada.


Thymus Gland, T-Lymphocyte Subsets, Animals, Mice, Inbred C57BL, Mice, Transgenic, Mice, Peptides, Receptors, Antigen, T-Cell, Ligands, Organ Culture Techniques, Lymphocyte Activation, Cell Differentiation, Calcium Signaling, Down-Regulation, Female, Male