Rebuilding T cell antigen receptor (TCR) nanoclusters and signaling across biomimetic membranes

Prof. Wolfgang Schamel (Institute of Biology III and BIOSS, University of Freiburg)

Jun.-Prof. Winfried Römer (Institute of Biology II and BIOSS, University of Freiburg)

The T cells of the immune system are important to fight against foreign pathogens. Naïve T cells, that have not yet met the pathogen, are not sensitive and thus require large amounts of antigen to become active and mount an immune response. When the T cells come across the same pathogen a second time, they are much more sensitive toward them. This is called immunological memory. We showed that the increased sensitivity is caused by a clustering of the T cell receptors (TCRs): In a naive cell the TCRs are expressed as monomers. In a memory T cell the TCRs are pre-clustered. This makes the memory T cells more sensitive and protects us from infections.

Using a synthetic approach in which we rebuild the TCR pre-clusters from TCR monomers in artificial liposomes, we discovered that the composition of the lipids of a membrane is responsible for TCR pre-clustering of the receptors. The lipid composition of a naive cell differs from that of a memory cell. Cholesterol is the key factor in this process, as it is present in higher concentrations in a memory cell. This higher concentration of cholesterol leads to the aggregation of the receptors, because the cholesterol joins them together like glue. Now we plan to extend our technologies to quantify TCR pre-clustering in biomimetic membranes.