The study investigates the role of MHC class II molecules in chickens, particularly focusing on the B2 haplotype known for its resistance to Marek’s disease virus (MDV). Using a novel in vitro infection system and immunopeptidomics, researchers found that the majority of viral peptide epitopes presented by chicken class II molecules arise from only four viral genes. The study also revealed an unprecedented decamer core motif in the BL2*02 molecule, which is dominantly expressed in chickens. This finding provides insights into the differential MHC-determined resistance to MDV and opens up potential avenues for vaccine development.