The Affinity of Elongated Membrane-Tethered Ligands Determines Potency of T Cell Receptor Triggering

The Affinity of Elongated Membrane-Tethered Ligands Determines Potency of T Cell Receptor Triggering

Blog Article

T lymphocytes are important mediators of adoptive immunity but the mechanism of T read more cell receptor (TCR) triggering remains uncertain.The interspatial distance between engaged T cells and antigen-presenting cells (APCs) is believed to be important for topological rearrangement of membrane tyrosine phosphatases and initiation of TCR signaling.We investigated the relationship between ligand topology and affinity by generating a series of artificial APCs that express membrane-tethered anti-CD3 scFv with different affinities (OKT3, BC3, and 2C11) in addition to recombinant class I and II pMHC molecules.The dimensions of membrane-tethered anti-CD3 and pMHC molecules were progressively increased by insertion of different extracellular domains.

In agreement with previous studies, elongation of pMHC molecules or low-affinity anti-CD3 scFv caused progressive loss of T cell activation.However, elongation of high-affinity ligands (BC3 and OKT3 scFv) did not abolish TCR phosphorylation and T cell activation.Mutation of key amino acids in OKT3 sex shop arles to reduce binding affinity to CD3 resulted in restoration of topological dependence on T cell activation.Our results show that high-affinity TCR ligands can effectively induce TCR triggering even at large interspatial distances between T cells and APCs.