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-aminoacid 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-␥) 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-␥ (P ‫؍‬ 0.02) and IL-4 (P ‫؍‬ 0.03) secretion was DRB1*0301. For MV-N, the allele with the strongest association with IFN-␥ 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.

Genetic studies of African populations: an overview on disease susceptibility and response to vaccines and therapeutics

“…As noted above, HLA variation has also been studied extensively in terms of susceptibility to the disease themselves (Tables 6, 7, Supplemental Tables). Relatively consistent Wndings have been reported for HLA associations with immunity induced by HBV vaccination (Kimman et al 2007;Milich and Leroux-Roels 2003;Thursz 2001); the HLA data on responses to other vaccinations, except measles (Ovsyannikova et al 2004c(Ovsyannikova et al , 2006a, are sparse. However, even less is published in relation to variation in non-HLA genes.…”

Vaccinomics: Current Findings, Challenges and Novel Approaches for Vaccine Development

“…Using mass spectrometry, we identified 13 immunogenic measles virus-derived DRB1*0301-bound peptides that may be potentially used in generating a new measles vaccine formulation, and these peptide epitopes were chosen to avoid our previously identified HLA polymorphic restrictions (57)(58)(59). By identifying such genetically restricted peptides, and using information regarding peptide/HLA promiscuity, including HLA supertypes, new multi-peptide vaccines administered with specific adjuvants could be developed and tested.…”

The wide diversity and complexity of peptides bound to class II MHC molecules

“…Surprisingly, despite such differences, the number of T cells responding to each peptide was about equal, implying that there are control mechanisms which level the response despite large variations in epitope display. Finally, some recent reports have identified naturally processed peptides from microbial proteins or tumor antigens recognized by CD4 + T cells which should be useful in designing peptide vaccination approaches [22][23][24].…”