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| Content Provider | PubMed Central |
|---|---|
| Author | Haan, Lolke De Hearn, Arron R. Rivett, A. Jennifer Hirst, Timothy R. |
| Copyright Year | 2002 |
| Abstract | Current immunization strategies, using peptide or protein antigens, generally fail to elicit cytotoxic-T-lymphocyte responses, since these antigens are unable to access intracellular compartments where loading of major histocompatibility complex class I (MHC-I) molecules occurs. In an attempt to circumvent this, we investigated whether the GM1 receptor-binding B subunit of Escherichia coli heat-labile toxin (EtxB) could be used to deliver class I epitopes. When a class I epitope was conjugated to EtxB, it was delivered into the MHC-I presentation pathway in a GM1-binding-dependent fashion and resulted in the appearance of MHC-I-epitope complexes at the cell surface. Importantly, we show that the efficiency of EtxB-mediated epitope delivery could be strikingly enhanced by incorporating, adjacent to the class I epitope, a 10-amino-acid segment from the C terminus of the DNA polymerase (Pol) of herpes simplex virus. The replacement of this 10-amino-acid segment by a heterologous sequence or the introduction of specific amino acid substitutions within this segment either abolished or markedly reduced the efficiency of class I epitope delivery. If the epitope was extended at its C terminus, EtxB-mediated delivery into the class I presentation pathway was found to be completely dependent on proteasome activity. Thus, by combining the GM1-targeting function of EtxB with the 10-amino-acid Pol segment, highly efficient delivery of exogenous epitopes into the endogenous pathway of class I antigen processing and presentation can be achieved. |
| Related Links | http://dx.doi.org/10.1128/iai.70.6.3249-3258.2002 |
| Ending Page | 3258 |
| Page Count | 10 |
| Starting Page | 3249 |
| File Format | |
| ISSN | 00199567 |
| e-ISSN | 10985522 |
| Journal | Infection and Immunity |
| Issue Number | 6 |
| Volume Number | 70 |
| Language | English |
| Publisher | American Society for Microbiology |
| Publisher Date | 2002-06-01 |
| Access Restriction | Open |
| Rights Holder | American Society for Microbiology |
| Subject Keyword | Immunology Microbiology Parasitology Infectious Diseases Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Infectious Diseases Parasitology Immunology Microbiology |
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