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. Author manuscript; available in PMC: 2016 Jun 1.
Published in final edited form as: Cancer Immunol Res. 2015 Mar 20;3(6):602–609. doi: 10.1158/2326-6066.CIR-15-0030

Figure 4. Proposed model of melanoma cell MHC class I trafficking in the context of MAP kinase pathway activation or inhibition.

Figure 4

Oncogenic activating BRAF mutations (e.g., V600E) in melanoma cells drive the rapid and constitutive internalization of MHC-I molecules from the cell surface and their subsequent sequestration within LAMP1-positive endolysosomal compartments (left). This redistribution process requires the conserved serine-335 phosphorylation site (S) found within the cytoplasmic tail of MHC-I. Pharmaceutical inhibition of MAPK signaling can inhibit MHC-I internalization, thus altering the equilibrium and resulting in reduced endolysosomal sequestration and enhanced MHC-I surface expression within hours (right). This augmented MHC-I surface expression in turn leads to increased tumor cell recognition and function of melanoma antigen-specific CD8+ T cells.