Minor or histocompatibility (H) antigens are recognized by CD4⁺ and CD8⁺ T lymphocytes as short polymorphic peptides associated with MHC molecules. They are the targets of graft versus host and graft versus leukemia responses following bone marrow transplantation between HLA-identical siblings. Several genes encoding class I–restricted minor H epitopes have been identified, but approaches used for these have proved difficult to adapt for cloning class II–restricted minor H genes. We have combined the unique antigen-presenting properties of dendritic cells and high levels of episomal expression following transfection of COS cells to identify a Y chromosome gene encoding two HY peptide epitopes, HYA^b and HYE^k.