Increased sensitivity of antigen-experienced T cells through the enrichment of oligomeric T cell receptor complexes.

08.09.2011

Kumar R, Ferez M, Swamy M, Arechaga I, Rejas MT, Valpuesta JM, Schamel WW, Alarcon B, van Santen HM.

Immunity. 2011;35(3):375-87

Immunity         online article

In the immune system signal transduction through the T cell receptor (TCR) is important to activate a T cell and thus initiate an immune response. In this BIOSS project, in collaboration with the group of Balbino Alarcon in Spain, we discovered one mechanism of how the sensitivity of this process is regulated. We took the observation that memory T cells are more sensitive to stimulation by antigen than naive T cells as the starting point of our study. We had previously shown that the TCR exists on the T cell surface as different-sized nanoclusters and that the large nanoclusters are preferentially activated in response to low antigen doses. In this publication we show by using BN-PAGE and electron microscopy that effector and memory T cells have more and larger TCR nanoclusters than their naive counterparts. Reconstitution of T cells and mice with a point mutant of the TCR’s CD3z subunit, which impairs nanocluster formation, demonstrated that the increased
size of TCR nanoclusters was directly responsible for the increased sensitivity of antigen-experienced T cells. We propose that an ‘‘avidity maturation’’ underlies T cell antigenic memory.