Hemagglutinin protein is a primary target of the measles virus-specific HLA-A2-restricted CD8+ T cell response during measles and after vaccination

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.