期刊
JOURNAL OF VIROLOGY
卷 78, 期 1, 页码 42-51出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.78.1.42-51.2004
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资金
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI048793, R03AI053592, R01AI033144, R37AI048793] Funding Source: NIH RePORTER
- NIAID NIH HHS [AI48793, R37 AI048793, R01 AI048793, AI33144, R03 AI053592, R01 AI033144, AI53592] Funding Source: Medline
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 DRBl*0301. For MV-N, the allele with the strongest association with IFN-gamma secretion was DRBl*1501 (P = 0.04), and the alleles with the strongest associations with IL-4 secretion were DRB1*1103 and DRBl*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.
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