Figure 6. Quality control of the αβTCR by assembly-dependent membrane integration.

Model for the assembly-dependent quality control mechanism in αβTCR biosynthesis. All chains except for the α-chain are properly integrated in the ER membrane co-translationally. Heterodimers between CD3γ and ε or CD3δ and ε form soon after their biosynthesis. Two pathways can be taken by the TCR α-chain. Either, the CD3δε heterodimer interacts with the α-chain and allows it to stably integrate into the ER membrane. Subsequently, the CD3δε-α and the CD3γε-β hetero-trimers can move in the membrane, assemble covalently, pair with the ζ dimer and be transported to the cell surface. Alternatively, newly synthesized α-chains that fail to assemble with the CD3δε heterodimer completely enter the ER lumen over time and their TM domains are recognized by the ER chaperone BiP allowing them to be targeted for ERAD. Some of the TCR α-chain its TM region is initially missed as a stop-transfer sequence and it directly enters the ER lumen to be degraded.