Commercial poultry operations produce and crowd billions of birds every year, which is a source of inexpensive animal protein. Commercial poultry is intensely bred for desirable production traits, and currently presents very low variability at the major histocompatibility complex. This situation dampens the advantages conferred by the MHC´s high genetic variability, and crowding generates immunosuppressive stress. We address the proteins of influenza A viruses directly and indirectly involved in host specificities. We discuss how mutants with increased virulence and/or altered host specificity may arise if few class I alleles are the sole selective pressure on avian viruses circulating in immunocompromised poultry. This hypothesis is testable with peptidomics of MHC ligands. Breeding strategies for commercial poultry can easily and inexpensively include high variability of MHC as a trait of interest, to help save billions of dollars as a disease burden caused by influenza and decrease the risk of selecting highly virulent strains.