Secreted HLA Fc-Fusion Profiles Immunopeptidome in Hypoxic PDAC and Cellular Senescence

Here, we describe a secreted HLA (sHLA) Fc-fusion construct for simple single HLA allele profiling in hypoxic pancreatic ductal adenocarcinoma (PDAC) and cellular senescence. This method streamlines sample preparation, enables temporal control, and provides allele-restricted target identification. Over 30,000 unique HLA-associated peptides were identified across two different HLA alleles and seven cell lines, with ~9,300 peptides newly discovered. The sHLA Fc-fusion capture technology holds potential to expedite immunopeptidomics and advance therapeutic interest in peptide-HLA complexes.