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

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.

Leucine-tRNA initiates at CUG start codons for protein synthesis and presentation by MHC class I.

Effective immune surveillance by cytotoxic T cells requires newly synthesized polypeptides for presentation by major histocompatibility complex (MHC) class I molecules. These polypeptides are produced not only from conventional AUG-initiated, but also from cryptic non-AUG-initiated, reading frames by distinct translational mechanisms. Biochemical analysis of ribosomal initiation complexes at CUG versus AUG initiation codons revealed that cells use an elongator leucine-bound transfer RNA (Leu-tRNA) to initiate translation at cryptic CUG start codons.