Meindert Lamers, Ilana Berlin, Jacques Neefjes  Current Biology 

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Antigen Presentation: Visualizing the MHC Class I Peptide-Loading Bottleneck  Meindert Lamers, Ilana Berlin, Jacques Neefjes  Current Biology  Volume 28, Issue 2, Pages R83-R86 (January 2018) DOI: 10.1016/j.cub.2017.11.059 Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 1 A structural view of the MHC class I antigen presentation pathway. Presentation of antigens by MHC class I molecules begins with degradation of cytosolic proteins into peptides by the 26S proteasome [13]. A small percentage of the resulting peptides escapes further processing by cytosolic proteases, such as TPP II [14] and LAP [15], and is transported across the ER membrane by the TAP transporter [16]. Here, in the ER lumen, peptides can be loaded onto MHC class I molecules [17] residing in the PLC, which also contains the key chaperones tapasin, ERp57, and calreticulin [3]. Peptides that fail to successfully bind to MHC class I are further processed by ER luminal peptidases ERAP1 [18] and/or PDI [19], or are transported back into the cytosol by the ERAD system [20] for complete degradation. Having acquired a suitable peptide, the MHC class I molecule exits the PLC by an unknown mechanism and traffics to the cell surface for presentation to the immune system. Structures of the indicated proteins are shown in surface representation. Current Biology 2018 28, R83-R86DOI: (10.1016/j.cub.2017.11.059) Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 2 Molecular arrangement of the MHC class I peptide-loading complex. The antigen-presenting MHC class I–β2m dimer is surrounded by the PLC chaperones calreticulin, tapasin, and ERp57, which aid in the loading of the peptide. A second MHC class I–β2m–chaperone complex (shown in light colours) is placed in a pseudo-symmetric arrangement. The Tap1/2 complex transports peptides over the ER membrane and is directly connected to the MHC class I–chaperone complex. Once loaded with a peptide, the MHC class I–β2m dimer is released from the PLC and transported to the plasma membrane for presentation. Current Biology 2018 28, R83-R86DOI: (10.1016/j.cub.2017.11.059) Copyright © 2017 Elsevier Ltd Terms and Conditions