To characterize the measles virus (MV)-specific T cell responses important for evaluation of measles vaccines, human leukocyte antigen (HLA)-A2-positive and -negative adults immunized with measles-mumps-rubella vaccine were studied. Both groups developed increases in antibody and in interferon (IFN)- gamma -producing cells in response to pooled hemagglutinin (H) and fusion peptides. HLA-A2-binding peptides were predicted for all MV-encoded proteins and confirmed by T2 cell stabilization. Twenty-nine peptides were tested, and 19 (6 from H) stimulated increased IFN- gamma secretion in a majority of vaccinees. Peptide-loaded HLA-A2 tetramers or immunoglobulin dimers documented MV-specific CD8+ T cell responses after vaccination and during measles and confirmed new A2 epitopes in H (250-259 and 516-525 aa) and matrix (M; 50-58 aa) protein and previously described epitopes in H (30-38 aa), M (211-219 aa), and nonstructural protein C (84-92 aa). No single peptide dominated the response. We conclude that H is an important stimulus for CD8+ T cell as well as for antibody responses in HLA-A2-positive individuals.