Super-Resolution Microscopy Unravels Localization of Human T Cell Receptors on Microvilli

Yunmin Jung, Chemical Physics, Weizmann Institute of Science, Rehovot, Israel
Inbal Riven, Chemical Physics, Weizmann Institute of Science, Rehovot, Israel
Sara Feigelson, Immunology, Weizmann Institute of Science, Rehovot, Israel
Ronen Alon, Immunology, Weizmann Institute of Science, Rehovot, Israel
Gilad Haran, Chemical Physics, Weizmann Institute of Science, Rehovot, Israel

Super-resolution microscopy is revolutionizing our understanding of molecular organization in living cells, enabling fluorescence imaging significantly beyond the optical diffraction limit. In this study we apply super-resolution techniques to map T-cell receptors (TCRs) in relation to the structure of the T-cell membrane. TCRs are membrane protein complexes that recognize antigens as part of the primary steps of adaptive immunity. The antigen-TCR recognition event and its consequences, culminating in the formation of the immunological synapse, have been extensively studied. In recent years, several reports have revealed that TCRs are clustered on T cell even before encountering antigens. However, the fact that the structure of the T cell membrane is dominated by microvilli protrusions is less spotlighted, and hence there is a lack of understanding of how microvilli may affect the 3D organization of TCRs on the T-cell membrane. The largest obstacle in studying microvilli is their thin and short structure. In this study, we obtain information on the surface topography and the organization of TCRs on the membrane of resting and effector human T cells by using two different and complementary super-resolution fluorescence methods. Strikingly, we find that TCR molecules are highly localized on microvilli and depleted on the cell body, a phenomenon that is likely to have important implications for their function during the immune response.