{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T19:27:01Z","timestamp":1766086021865},"reference-count":33,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2002,6,1]],"date-time":"2002-06-01T00:00:00Z","timestamp":1022889600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2002,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>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<jats:italic>Escherichia coli<\/jats:italic>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.<\/jats:p>","DOI":"10.1128\/iai.70.6.3249-3258.2002","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:09:29Z","timestamp":1027764569000},"page":"3249-3258","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":33,"title":["Enhanced Delivery of Exogenous Peptides into the Class I Antigen Processing and Presentation Pathway"],"prefix":"10.1128","volume":"70","author":[{"given":"Lolke","family":"de Haan","sequence":"first","affiliation":[{"name":"Departments of Pathology &amp; Microbiology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arron R.","family":"Hearn","sequence":"additional","affiliation":[{"name":"Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. 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