Response of primed human PBMC to synthetic peptides derived from hepatitis B virus envelope proteins: a search for promiscuous epitopes

Abstract

This investigation was aimed at identifying effective T helper cell epitopes to the hepatitis B virus in humans. A panel of synthetic peptides that represent the hepatitis B virus whole envelope proteins was examined for their capability to stimulate peripheral blood mononuclear cells from human subjects infected with hepatitis B virus naturally. In addition, a large number of subjects were examined and their human leukocyte antigen (HLA) class II allele types were identified to determine whether the helper T cell epitope is specific for a particular HLA allele or 'promiscuous'. The peptides of the amino acid residues 52-67, 110-125, 190-205, and 228-243 appeared to be immunogenic, and particularly, the 52-67 residue was the most promiscuous epitope peptide. These results would contribute to the better understanding of the helper T cell responses to the hepatitis B virus and provide a useful way in designing epitope-based vaccines and future therapeutic strategies.

Specificities of Human CD4 + T Cell Responses to an Inactivated Flavivirus Vaccine and Infection: Correlation with Structure and Epitope Prediction

“…6), peptides of the TM domain were among the most frequently predicted, but when they were analyzed experimentally, they failed to be associated with a similar dominance (40,(59)(60)(61)(62)(63)(64)(65)(66)(67). There was a single exception, the N-terminal TM domain of HBsAg, which is described as being immunodominant in humans (50,(55)(56)(57)(58). At least in the context of full-length HBsAg, however, this sequence element has been described to lie outside the membrane (81,82) and therefore may have characteristics that differ from conventional TM domains.…”

“…To analyze whether predicted immunodominance is a general feature of viral transmembrane (TM) protein domains, we performed CD4 ϩ T cell epitope predictions for envelope proteins of viruses for which experimental data (including those for TM domain-derived peptides) were available. This included envelope proteins of HBV (50,(55)(56)(57)(58), influenza virus (40,59,60), VACV-EV (61, 62), SARS-coronavirus (63, 64), HSV-1 (65), and HIV (66) as well as YF (67) and DEN (68) viruses. For each of these viruses the TM domain-derived peptides (both at the C terminus as in type I and at the N terminus as in type II membrane proteins) were among those with the highest prediction frequency (Fig.…”

“…However, in none of these cases was a dominant CD4 ϩ T cell response to such peptides found experimentally, with a single exception: one of the four TM domains (proximal to the N terminus, amino acids 182 to 202) ( Fig. 6) of hepatitis B virus surface antigen (HBsAg) contained CD4 ϩ T cell epitopes that were described to be immunodominant in humans (50,(55)(56)(57)(58). In conclusion, the high predictive values for CD4 ϩ T cell epitopes in the TM domains of viral envelope proteins is not confirmed by experimental data in most instances.…”

A Novel Method of Transcriptional Response Analysis to Facilitate Drug Repositioning for Cancer Therapy

“…We used the dose-response data derived from the Developmental Therapeutics Program (DTP) of NCI/NIH (31) to validate our hypothesis. Checking the dose-response curves for raloxifene, tamoxifene, paclitaxel, and fulvestrant (Figure 5), we found that all of the four drugs with considered dosages (lower than 10 μ M ) have a significant inhibition on the cell growth.…”

“…In contrast, the curve for fulvestrant indicates that at higher dosages fulvestrant does not induce the cell death. The data source is Developmental Therapeutics Program (DTP) of NCI/NIH (31). …”