A window of opportunity for cooperativity in the T Cell Receptor
Martin-Blanco N, Blanco R, Alda-Catalinas C, Bovolenta ER, Oeste CL, Palmer E, Schamel WW, Lythe G, Molina-París C, Castro M, Alarcon B.
In this BIOSS publication we have studied the consequences of the T-cell antigen receptor (TCR) nanoclusters in cooperation with Madrid. TCR nanoclusters could provide a framework for inter-TCR cooperativity upon peptide antigen-major histocompatibility complex (pMHC) binding. We used soluble pMHC oligomers and find that initial binding events favour subsequent pMHC binding to additional TCRs. TCRs exist in either the Resting conformtion or in the Active conformation. By disrupting nanoclusters and hampering the Active conformation, we show that TCR cooperativity is consistent with TCR nanoclusters adopting the Active state in a coordinated manner. Preferential binding of pMHC to the Active TCR at the immunological synapse suggests that there is a transient time frame for signal amplification in the TCR, allowing the T cells to keep track of antigen quantity and binding time.
