Structural Model of the Extracellular Assembly of the TCR-CD3 Complex.

ABSTRACT: Antigen recognition of peptide-major histocompatibility complexes (pMHCs) by T cells, a key step in initiating adaptive immune responses, is performed by the T cell receptor (TCR) bound to CD3 heterodimers. However, the biophysical basis of the transmission of TCR-CD3 extracellular interaction into a productive intracellular signaling sequence remains incomplete. Here we used nuclear magnetic resonance (NMR) spectroscopy combined with mutational analysis and computational docking to derive a structural model of the extracellular TCR-CD3 assembly. In the inactivated state, CD3?? interacts with the helix 3 and helix 4-F strand regions of the TCR C? subunit, whereas CD3?? interacts with the F and C strand regions of the TCR C? subunit in this model, placing the CD3 subunits on opposing sides of the TCR. This work identifies the molecular contacts between the TCR and CD3 subunits, identifying a physical basis for transmitting an activating signal through the complex.

SUBMITTER: Natarajan A 

PROVIDER: S-EPMC4902171 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature