T cell activation is crucial for the development of specific immune reactions. It requires physical
contact between T cells and antigen-presenting cells (APC). Since these cells are initially located
at distinct positions in the body, they have to migrate and find each other within secondary lymphoid organs.
After encountering each other both cells have to maintain a close membrane contact sufficiently long
to ensure successful signaling. Thus, there is the necessity to temporarily synchronize the motile behavior
of these cells. Initially, it had been proposed that during antigen recognition, T cells receive a stop
signal and maintain a stable contact with APC for several hours when an appropriate APC has been encountered.
However, direct cell observation via time-lapse microscopy in vitro and in vivo has revealed a different
picture. While long contacts can be observed, many interactions appear to be very short and sequential
despite efficient signaling. Thus, two concepts addressing the biophysics of T cell activation have
emerged. The single encounter model proposes that after a period of dynamic searching, a T cell
stops to interact with one appropriately presenting APC until signaling is completed. The serial encounter
model suggests that T cells are able to collect a series of short signals by different APC until
a critical activation threshold is achieved. Future research needs to clarify the relative importance
of short and dynamic versus long-lived T cell–APC encounters for the outcome of T cell activation.
Furthermore, a thorough understanding of the molecular events underlying the observed complex motility
patterns will make these phenomena amenable for intervention, which might result in the identification of
new types of immune modulating drugs.
Biophysics Cell–cell interaction DC T cell activation
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