Structure of a fully assembled tumor-specific T cell receptor ligated by pMHC
Lukas Sušac, Mai Tuyet Vuong, Christoph Thomas, Sören von Bülow, Caitlin O’Brien‐Ball, Ana Mafalda Santos, Ricardo A. Fernandes, Gerhard Hummer, Robert Tampé, Simon J. Davis
Abstract
complex bound to a melanoma-specific human class I pMHC at 3.08 Å resolution. The antigen-bound complex comprises 11 subunits stabilized by multivalent interactions across three structural layers, with clustered membrane-proximal cystines stabilizing the CD3-εδ and CD3-εγ heterodimers. Extra density sandwiched between transmembrane helices reveals the involvement of sterol lipids in TCR assembly. The geometry of the pMHC/TCR complex suggests that efficient TCR scanning of pMHC requires accurate pre-positioning of T cell and antigen-presenting cell membranes. Comparisons of the ligand-bound and unliganded receptors, along with molecular dynamics simulations, indicate that TCRs can be triggered in the absence of spontaneous structural rearrangements.