Thus HLA-E is highly evolved to bind specifically to the class-I leader peptide.(41) The class-I leader peptide or microbial (cytomegalovirus, human immunodeficiency virus, Hep-C, and others) peptides may not be available when tumor cells and virally infected cells have downregulated HLA-I expression.(42) Furthermore, viruses can inhibit the function of TAP(43,44), which is required to transport leader peptides, and cleaved from nascent class-I molecules, from the cytoplasm into the ER. The gene discussed is HLA-E; the disease is neoplasm.