Transport of antigen loaded MHC II molecules to surface

Stable Identifier
Reaction [omitted]
Homo sapiens
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Once MHC class II-peptide complexes are formed, they must be transported back to the cell surface. It is unclear how this occurs. LEs/lysosomes with peptide loaded MHC II molecules may move in a bidirectional manner in a stop-and-go fashion along microtubules to the plasma membrane, driven by the activities of the oppositely-directed motor proteins dynein and kinesin (Wubbolts et al. 1996, 1999, Chow et al. 2002, Rocha & Neefjes 2007). Ultimately, LEs/lysosomes fuse to the plasma membrane delivering the MHC II-peptide complexes to the surface (Raposo et al. 1996, Rocha & Neefjes 2007). RAB7-GTP present on LEs/lysosome membrane interacts with Rab7-interacting lysosomal protein (RILP) and oxysterol-binding protein-related protein 1L (ORP1L) to form a tripartite RILP-Rab7-ORP1L complex. RILP binds to the p150 dynactin subunit to recruit the dynein or kinesin motor proteins. ORP1L recruits this complex to betaIII spectrin domains, which appears to be critical for dynein motor activation and transport of LEs/lysosome vesicles to the cell periphery (Johansson et al. 2007, Rocha & Neefjes 2008).
Literature References
PubMed ID Title Journal Year
18046453 MHC class II molecules on the move for successful antigen presentation

Neefjes, J, Rocha, N

EMBO J 2008
10036229 Opposing motor activities of dynein and kinesin determine retention and transport of MHC class II-containing compartments

Neefjes, J, Reits, E, Vallee, RB, Fernandez-Borja, M, Dusseljee, S, Jordens, I, Wubbolts, R, Echeverri, C

J Cell Sci 1999
8642258 B lymphocytes secrete antigen-presenting vesicles

Harding, CV, Liejendekker, R, Stoorvogel, W, Nijman, HW, Geuze, HJ, Melief, CJ, Raposo, G

J Exp Med 1996
19564404 Cholesterol sensor ORP1L contacts the ER protein VAP to control Rab7-RILP-p150 Glued and late endosome positioning

Janssen, H, Janssen, L, Rocha, N, Zwart, W, Neefjes, J, Kuijl, C, Houben, D, van der Kant, R

J. Cell Biol. 2009
8909537 Direct vesicular transport of MHC class II molecules from lysosomal structures to the cell surface

Neefjes, J, Tulp, A, Calafat, J, Fernandez-Borja, M, Janssen, H, Verwoerd, D, Dusseljee, S, Wubbolts, R, Oomen, L

J Cell Biol 1996
17283181 Activation of endosomal dynein motors by stepwise assembly of Rab7-RILP-p150Glued, ORP1L, and the receptor betalll spectrin

Olkkonen, VM, Kuijl, C, Johansson, M, Neefjes, J, Zwart, W, Janssen, L, Jordens, I, Rocha, N

J Cell Biol 2007
12198549 Dendritic cell maturation triggers retrograde MHC class II transport from lysosomes to the plasma membrane

Toomre, D, Mellman, I, Chow, A, Garrett, W

Nature 2002
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