biostudies-literatureUnknown30(6)Darwish MDespite the need to monitor the impact of Cancer Immunotherapy (CI)/Immuno-Oncology (IO) therapeutics on neoantigen-specific T-cell responses, very few clinical programs incorporate this aspect of immune monitoring due to the challenges in high-throughput (HTP) generation of Major Histocompatibility Complex Class I (MHCI) tetramers across a wide range of HLA alleles. This limitation was recently addressed through the development of MHCI complexes with peptides containing a nonnatural UV cleavable amino acid (conditional MHCI ligands) that enabled HTP peptide exchange upon UV exposure. Despite this advancement, the number of alleles with known conditional MHCI ligands is limited. We developed a novel workflow to enable identification and validation of conditional MHCI ligands across a rangeProtein science : a publication of the Protein Society1169-1183https://www.ebi.ac.uk/biostudies/studies/S-EPMC8138534biostudies-literatureHigh-throughput identification of conditional MHCI ligands and scaled-up production of conditional MHCI complexes.PMC8138534Li HFranke YLi JChan PWichner SDarwish MBlanchette CChang JCTam CfalseHigh-throughput identification of conditional MHCI ligands and scaled-up production of conditional MHCI complexes.Despite the need to monitor the impact of Cancer Immunotherapy (CI)/Immuno-Oncology (IO) therapeutics on neoantigen-specific T-cell responses, very few clinical programs incorporate this aspect of immune monitoring due to the challenges in high-throughput (HTP) generation of Major Histocompatibility Complex Class I (MHCI) tetramers across a wide range of HLA alleles. This limitation was recently addressed through the development of MHCI complexes with peptides containing a nonnatural UV cleavable amino acid (conditional MHCI ligands) that enabled HTP peptide exchange upon UV exposure. Despite this advancement, the number of alleles with known conditional MHCI ligands is limited. We developed a novel workflow to enable identification and validation of conditional MHCI ligands across a range2021-01-01T00:00:00Z2021 Jun2026-06-04T09:27:02.264Z2025-04-06T03:52:41.014ZS-EPMC81385343384013710.1002/pro.4082