Characterization of HLA-A*33:03 epitopes via immunoprecipitation and LC-MS/MS

Human leukocyte antigen (HLA) class I has more than 18,000 alleles, each of which binds to a set of unique peptides from the cellular degradome. Deciphering the interaction between antigenic peptides and HLA proteins is crucial for understanding immune responses in autoimmune diseases and cancer. In this study, we aimed to characterize the peptidome that binds to HLA-A*33:03, which is one of the most prevalent HLA-A alleles in the Northeast Asian population, but poorly studied. For this purpose, we analyzed the HLA-A*33:03 monoallelic B cell line using immunoprecipitation of HLA-A and peptide complexes, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this study, we identified 5731 unique peptides that were associated with HLA A*33:03, and experimentally validated the affinity of 40 peptides for HLA-A*33:03 and their stability in HLA A*33:03-peptides complexes. To our knowledge, this study represents the largest dataset of peptides associated with HLA-A*33:03. Also, this is the first study in which HLA A*33:03-associated peptides were experimentally validated.

Automated summary

This study aimed to characterize the peptidome that binds to HLA-A*33:03, identifying 5731 unique peptides associated with this allele and experimentally validating the affinity and stability of 40 peptides. It represents the largest dataset of peptides linked to HLA-A*33:03 and the first experimental validation of HLA A*33:03-associated peptides.