Loss of ribosomal protein uL14 enables tumor escape from T cell immunosurveillance.

Abstract

The presentation of peptides on HLA molecules is essential to CD8⁺ T cell responses. Here, we show that loss of uL14 significantly downregulates the expression of antigen processing and presentation (APP) components in melanoma cell lines. Peptides generated following knockdown show different characteristics, with altered peptide charge, and differences in anchor residue positions. These peptides also have lower predicted binding to the HLA alleles and a shorter predicted HLA-peptide complex half-life. These result in a functional difference in APP, and knockdown of uL14 causes a reduction in the ability of CD8⁺ T cells to recognize and kill melanoma cells in a co-culture assay. Together, our data suggest that loss of uL14 alters the peptide pool available for presentation and thus may act as an escape mechanism from tumor immune surveillance.