Nanoclusters of the resting T cell antigen receptor (TCR) localize to non-raft domains

20.12.2014

Beck-García K, Beck-García E, Bohler S, Zorzin C, Sezgin E, Levental I, Alarcón B, Schamel WW.

Biochim Biophys Acta. 2015;1853(4):802-9

The T cell antigen receptor (TCR) orchestrates immune responses and thus to understand ist functioning is of high interest. Previously we could show that the TCR is not randomly distributed but instead forms pre-formed oligomers called nanoclusters. Furthermore, we demonstrated by a previous BIOSS publication that membrane lipids, namely cholesterol and sphingomyelin, contribute to TCR nanoclustering. However, the identity of the membrane microdomain in which the TCR resides remained controversial. Using a GFP-labelled TCR we show in this BIOSS publication that the resting TCR localised in the disordered domain of PM spheres (PMSs) and giant PM vesicles (GPMVs). Likewise, single and nanoclustered TCRs were present in the high-density fractions in sucrose gradients. Both findings are indicative of non-raft localization. We discuss possible mechanisms of TCR nanoclustering - protein and lipid-based.