Mechanisms of T cell motility and arrest: Deciphering the relationship between intra- and extracellular determinants

T lymphocytes are capable of rapid motility in vitro and in vivo. Upon antigen recognition, they may stop crawling and form a stable cell-cell contact called the 'immunological synapse' (IS). However, it is becoming clear that this outcome may not occur with the reliability that was once presumed. T cells, particularly naïve cells, are apparently triggered partly 'on the fly' during short contacts with peptide-MHC (pMHC) bearing antigen-presenting cells (APCs) and are also influenced in both activity and synapse duration by a multitude of external cues. Underlying the emerging issues is a paucity of data concerning the cell biology of T lymphocytes. Here, we review the molecular mechanisms of crawling and adhesion versus the various potential modes of 'stopping' in T lymphocytes. Both motility and arrest involve similar processes: adhesion, actin elongation and internal tension control, but with different coordination. We will attempt to integrate this with the known and potential external cues that signal for T cell motility versus stopping to form a synapse in vivo. Finally, we discuss how this interplay may give rise to unexpectedly complex motile and morphological behavior.