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.

In experiments where T cells interact with antigen-presenting-cells or supported bilayers bearing specific peptide-major-histocompatibility-complex (pMHC) molecules, T cell receptors (TCR) have been shown to form stable micrometer-scale clusters that travel from the periphery to the center of the contact region. pMHC molecules bind TCR on the opposing surface but the pMHC-TCR bond is weak and therefore pMHC can be expected to serially bind and unbind from TCR within the contact region. Using a novel mathematical analysis, we examine serial engagement of mobile clustered TCR by a single pMHC molecule. We determine the time a pMHC can be expected to remain within a TCR cluster. This also allows us to estimate the number of clustered TCR that are serially bound, and the distance a pMHC is transported by the clustered TCR. We find that TCR-pMHC binding alone does not allow substantial serial engagement of TCR and that the pMHC molecules are usually not transported to the center of the contact region by a single TCR cluster. We show that the presence of TCR coreceptors such as CD4 and CD8, or pMHC dimerization on the antigen-presenting cells, can substantially increase serial engagement and directed transport of pMHC. Finally, we analyze the effects of multiple TCR microclusters, showing that the size of individual clusters only weakly affects our prediction of TCR serial engagement by pMHC. Throughout, we draw parameter estimates from published data.

Original publication




Journal article


Biophys J

Publication Date





3447 - 3460


Dimerization, Histocompatibility Antigens, Lymphocyte Activation, Oligopeptides, Protein Binding, Protein Transport, Receptors, Antigen, T-Cell, Time Factors