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.
journal_name
Infect Immunjournal_title
Infection and immunityauthors
De Haan L,Hearn AR,Rivett AJ,Hirst TRdoi
10.1128/iai.70.6.3249-3258.2002keywords:
subject
Has Abstractpub_date
2002-06-01 00:00:00pages
3249-58issue
6eissn
0019-9567issn
1098-5522journal_volume
70pub_type
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.33.1.130-135.1981
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
pub_type: 杂志文章
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journal_title:Infection and immunity
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pub_type: 杂志文章
doi:10.1128/IAI.10.1.1-5.1974
更新日期:1974-07-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.22.1.5-9.1978
更新日期:1978-10-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
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更新日期:1988-10-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2006-09-01 00:00:00
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pub_type: 杂志文章
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journal_title:Infection and immunity
pub_type: 杂志文章
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更新日期:1975-04-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.41.2.858-860.1983
更新日期:1983-08-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/IAI.00601-10
更新日期:2010-12-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.63.10.4063-4071.1995
更新日期:1995-10-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
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journal_title:Infection and immunity
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.56.3.582-588.1988
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journal_title:Infection and immunity
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journal_title:Infection and immunity
pub_type: 杂志文章
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journal_title:Infection and immunity
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journal_title:Infection and immunity
pub_type: 杂志文章
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journal_title:Infection and immunity
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更新日期:1999-05-01 00:00:00
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pub_type: 杂志文章
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更新日期:1994-11-01 00:00:00
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