title: Identification and characterization of novel, naturally processed measles virus class II HLA-DRB1 peptides.
abstract: Previously, we identified a naturally processed and presented measles virus (MV) 19-amino-acid peptide, ASDVETAEGGEIHELLRLQ (MV-P), derived from the phosphoprotein and eluted from the human leukocyte antigen (HLA) class II molecule by using mass spectrometry. We report here the identification of a 14-amino-acid peptide, SAGKVSSTLASELG, derived from the MV nucleoprotein (MV-N) bound to HLA-DRB1*0301. Peripheral blood mononuclear cells (PBMC) from 281 previously vaccinated measles-mumps-rubella II (MMR-II) subjects (HLA discordant) were studied for peptide recognition by T cells. Significant gamma interferon (IFN-gamma) responses to MV-P and MV-N peptides were observed in 55.9 and 15.3% of subjects, respectively. MV-P- and MV-N-specific interleukin-4 (IL-4) responses were detected in 19.2 and 23.1%, respectively, of PBMC samples. Peptide-specific cytokine responses and HLA-DRB1 allele associations revealed that, for the MV-P peptide, the allele with the strongest association with both IFN-gamma (P = 0.02) and IL-4 (P = 0.03) secretion was DRB1*0301. For MV-N, the allele with the strongest association with IFN-gamma secretion was DRB1*1501 (P = 0.04), and the alleles with the strongest associations with IL-4 secretion were DRB1*1103 and DRB1*1303 (P = 0.01). These results indicate that HLA class II MV proteins can be processed, presented, and identified, and the ability to generate cell-mediated immune responses can be demonstrated. This information is promising for new vaccine design strategies with peptide-based vaccines.
authors.affiliation: Mayo Vaccine Research Group, Mayo Clinic and College of Medicine, Rochester, Minnesota 55905, USA.
authors.forename: Inna G
authors.initials: IG
authors.lastname: Ovsyannikova
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Johnson
authors.forename: David C
authors.initials: DC
authors.lastname: Muddiman
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Poland
mesh_terms: D000483:Alleles; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D006684:HLA-DR Antigens / Q000737:chemistry / Q000378:metabolism*; D059811:HLA-DRB1 Chains; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D008457:Measles / Q000276:immunology / Q000517:prevention & control; D008459:Measles virus / Q000276:immunology* / Q000378:metabolism; D022542:Measles-Mumps-Rubella Vaccine / Q000008:administration & dosage; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; D022542:Measles-Mumps-Rubella Vaccine; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010455:Peptides; D014764:Viral Proteins; C058314:nucleoprotein, Measles virus; D015847:Interleukin-4; D007371:Interferon-gamma