Multiple interactions contribute to the stability of the MHCI peptide-loading complex. Central to the PLC is Tpsn, which transmembrane domain interacts with TAP, forms disulfide bond with ERp57 and interact with the alpha2/3 domain of the heavy chain (HC). CRT binds both the HC alpha1 domain N-linked glycan and ERp57.

Calnexin (CNX) mediates the early folding stage of the HC prior to its association with b2M (1 and 2). The HC oxidation happens during this time and PDI and ERp57 facilitates this process (1). Upon proper oxidation and pairing with b2M, CNX is replace by CRT (3a). In parallel, newly synthesized Tpsn associates with TAP before forming a disulfide bound with ERp57 (3b). Rapidly, HC/b2M/CRT subcomplexes join the Tpsn/ERp57/TAP subcomplexes forming the PLC.

The presentation of pMHCI to CD8+ T cell starts by proteasomal antigen degradation and their subsequent trimming by a panel of aminopeptidases (1). Those peptides are then translocated to the ER lumen (2) and through a tapasin-dependent manner, the loading complex facilitates the generation of highly stable pMHCIs (3), leading to the release of loaded MHCIs and CRT from the PLC (4). After a transit to the Golgi (5), the MHCIs gain access to the plasma membrane and may present its associated-peptide to cognate CD8+ T cells (6).