DC Biology

One of the key events in immune response is priming of T cells by the so-called antigen presenting cells, whereby a specific antigen-specific population of T cells expand and drive the immune response. As with most of the body functions immune response is also dependent on variety of such cell-to-cell crosstalks. Conventionally biochemical cues are implicated in mediating these cellular crosstalks. During T cell priming specific protein fragments (antigenic peptides) are loaded on specific molecules (MHC molecules) on the surface of the antigen presenting cells, which are then recognised by a receptor complex on T cells (T cell receptor or TCR complex). On recognition T cells are activated and start proliferate, thus building up an army (clone) of similar T cells all of which can recognise the same antigen (clonal expansion). Scientists can investigate T cell activation in the absence of any antigen presenting cells outside the body in plastic culture plates, which is done by adding specific antibodies against few components of TCR complex. Interestingly, these antibodies give best results when they are immobilized on a solid matrix. This led to the hypothesis that some amount of physical drag on the cell membrane may be essential for T cell activation. This may be provided by the receptor-crosstalk between antigen presenting cells and T cells in physiological contexts and by the solid matrix-imobilized antibodies in the artificial experimental set-up. The study done by Ms. Chinky Liu, a senior research fellow in DClabIICB, has identified that this physical stretch or drag on the T cell membrane is sensed by a mechanosensing protein on the T cell membrane, called Piezo1. Piezo proteins are professional mechanosensors that were discovered in 2010 by Prof. Ardem Patapoutian's laboratory in Scripps Research Institute in USA. Till date these cell surface proteins have been implicated varied phyiological events like sensing of gentle touch by neurons, differentiation of cartilages, volume regulation of red blood cells, maintenance of blood pressure etc. This study provides the first report for an essential role of mechanical cues on cell membrane sensed by Piezo1 in our immune system. It also counters the conventional ideas centered around chemical sensing being the key drivers of all cellular crosstalks in the immune system. Piezo1 may be required not only for T cell activation, but also for T cell development, though it remains to be explored. This finding paves the way for more such studies that should explore the role of mechanical forces and the Piezo mechanosensors in immune system functioning.

(For details read the research article here.)