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: Inna G Ovsyannikova, Kenneth L Johnson, David C Muddiman, Robert A Vierkant, Gregory A Poland
• Journal: Journal of virology (J Virol) Vol. 78 Issue 1 Pg. 42-51 (Jan 2004) ISSN: 0022-538X [Print] United States
• PMID: 14671086 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cytokines
• HLA-DR Antigens
• HLA-DRB1 Chains
• HLA-DRB1*03:01 antigen
• Measles-Mumps-Rubella Vaccine
• Nucleocapsid Proteins
• Nucleoproteins
• Peptides
• Viral Proteins
• nucleoprotein, Measles virus
• Interleukin-4
• Interferon-gamma

Topics

• Alleles
• Cytokines (biosynthesis, genetics)
• HLA-DR Antigens (chemistry, metabolism)
• HLA-DRB1 Chains
• Humans
• Interferon-gamma (biosynthesis, genetics)
• Interleukin-4 (biosynthesis, genetics)
• Measles (immunology, prevention & control)
• Measles virus (immunology, metabolism)
• Measles-Mumps-Rubella Vaccine (administration & dosage)
• Nucleocapsid Proteins
• Nucleoproteins (chemistry, immunology, metabolism)
• Peptides (chemical synthesis, chemistry, immunology, metabolism)
• T-Lymphocytes (immunology)
• Viral Proteins (chemistry, immunology, metabolism)