%0 Journal Article
%T A TCR mechanotransduction signaling loop induces negative selection in the thymus
%J -
%D 2018
%R https://doi.org/10.1038/s41590-018-0259-z
%X The T cell antigen receptor (TCR) expressed on thymocytes interacts with self-peptide major histocompatibility complex (pMHC) ligands to signal apoptosis or survival. Here, we found that negative-selection ligands induced thymocytes to exert forces on the TCR and the co-receptor CD8 and formed cooperative TCR每pMHC每CD8 trimolecular ＆catch bonds＊, whereas positive-selection ligands induced less sustained thymocyte forces on TCR and CD8 and formed shorter-lived, independent TCR每pMHC and pMHC每CD8 bimolecular ＆slip bonds＊. Catch bonds were not intrinsic to either the TCR每pMHC or the pMHC每CD8 arm of the trans (cross-junctional) heterodimer but resulted from coupling of the extracellular pMHC每CD8 interaction to the intracellular interaction of CD8 with TCR每CD3 via associated kinases to form a cis (lateral) heterodimer capable of inside-out signaling. We suggest that the coupled trans每cis heterodimeric interactions form a mechanotransduction loop that reinforces negative-selection signaling that is distinct from positive-selection signaling in the thymus
%U https://www.nature.com/articles/s41590-018-0259-z