P-stalk ribosomes act as master regulators of cytokine-mediated processes

HLA Class I antigen processing and presentation (APP) is a highly regulated process that enables CD8+ T cell immunosurveillance. APP begins with the ribosomal synthesis of a source antigen, yet the role of ribosomes, particularly specialized ribosomes, in antigen presentation is poorly understood. Here, we show that the presence of the “P-stalk” on the ribosome enhances antigen presentation. The addition of the P-stalk to the ribosome is stimulated by cytokines that upregulate APP components, and knockdown of one of the P-stalk proteins (P1) reduces T cell recognition of tumor cells. Mechanistically, we show that P1-containing ribosomes exhibit enhanced translation of HLA Class I molecules and accessory APP components. Finally, analysis of patient data reveals that the mRNA expression of the P-stalk proteins positively correlates with CD8+ T cell infiltration, a trend not seen for other ribosomal proteins. In all, we demonstrate that the presence of the P-stalk defines a specialized ribosome population that enhances antigen presentation, something that may be exploited by cancer cells to escape immunosurveillance. Ribosome profiling with HA-tagged RPLP1 (P1) and RPL22 (eL22) ribosomal proteins in cytokine treated Mel624 melanoma cell lines.