Presentation of Cryptic Peptides by MHC Class I Is Enhanced by Inflammatory Stimuli

Abstract

Cytolytic T cells eliminate infected or cancer cells by recognizing peptides presented by MHC class I molecules on the cell surface. The antigenic peptides are derived primarily from newly synthesized proteins including those produced by cryptic translation mechanisms. Previous studies have shown that cryptic translation can be initiated by distinct mechanisms at non-AUG codons in addition to conventional translation initiated at the canonical AUG start codon. In this study, we show that presentation of endogenously translated cryptic peptides is enhanced by TLR signaling pathways involved in pathogen recognition as well as by infection with different viruses. This enhancement of cryptic peptides was caused by proinflammatory cytokines, secreted in response to microbial infection. Furthermore, blocking these cytokines abrogated the enhancement of cryptic peptide presentation in response to infection. Thus, presentation of cryptic peptides is selectively enhanced during inflammation and infection, which could allow the immune system to detect intracellular pathogens that might otherwise escape detection because of inhibition of conventional host translation mechanisms.