title: Hemagglutinin protein is a primary target of the measles virus-specific HLA-A2-restricted CD8+ T cell response during measles and after vaccination.
abstract: 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.
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
authors.forename: Martin O
authors.initials: MO
authors.lastname: Ota
authors.forename: Zaza
authors.initials: Z
authors.lastname: Ndhlovu
authors.forename: SangKon
authors.initials: S
authors.lastname: Oh
authors.forename: Sucheep
authors.initials: S
authors.lastname: Piyasirisilp
authors.forename: Jay A
authors.initials: JA
authors.lastname: Berzofsky
authors.forename: William J
authors.initials: WJ
authors.lastname: Moss
authors.forename: Diane E
authors.initials: DE
authors.lastname: Griffin
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology; D006389:Hemagglutinins, Viral / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis; D008297:Male; D008457:Measles / Q000276:immunology* / Q000517:prevention & control; D008459:Measles virus / Q000276:immunology*; D022542:Measles-Mumps-Rubella Vaccine / Q000276:immunology*; D013997:Time Factors; D014763:Viral Matrix Proteins / Q000276:immunology / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D006389:Hemagglutinins, Viral; D022542:Measles-Mumps-Rubella Vaccine; D014763:Viral Matrix Proteins; C032397:hemagglutinin protein G, measles virus; D007371:Interferon-gamma