TAP-independent presentation of CTL epitopes by Trojan antigens

J. Lu, P. J. Wettstein, Y. Higashimoto, E. Appella, E. Celis

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

The majority of CTL epitopes are derived from intracellular proteins that are degraded in the cytoplasm by proteasomes into peptides that are transported into the endoplasmic reticulum by the TAP complex. These peptides can be further processed into the optimal size (8-10 residues) for binding with nascent MHC class I molecules, generating complexes that are exported to the cell surface. Proteins or peptides containing CTL epitopes can be introduced into the cytoplasm of APCs by linking them to membrane-translocating Trojan carriers allowing their incorporation into the MHC class I Ag-processing pathway. The present findings suggest that these "Trojan" Ags can be transported into the endoplasmic reticulum in a TAP-independent way where they are processed and trimmed into CTL epitopes. Furthermore, processing of Trojan Ags can also occur in the trans-Golgi compartment, with the participation of the endopeptidase furin and possibly with the additional participation of a carboxypeptidase. We believe that these findings will be of value for the design of CTL-inducing vaccines for the treatment or prevention of infectious and malignant diseases.

Original languageEnglish (US)
Pages (from-to)7063-7071
Number of pages9
JournalJournal of Immunology
Volume166
Issue number12
DOIs
StatePublished - Jun 15 2001

Fingerprint

Epitopes
Antigens
Endoplasmic Reticulum
Peptides
Cytoplasm
Furin
Carboxypeptidases
Endopeptidases
Proteasome Endopeptidase Complex
Communicable Diseases
Proteins
Vaccines
Membranes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

TAP-independent presentation of CTL epitopes by Trojan antigens. / Lu, J.; Wettstein, P. J.; Higashimoto, Y.; Appella, E.; Celis, E.

In: Journal of Immunology, Vol. 166, No. 12, 15.06.2001, p. 7063-7071.

Research output: Contribution to journalArticle

Lu, J, Wettstein, PJ, Higashimoto, Y, Appella, E & Celis, E 2001, 'TAP-independent presentation of CTL epitopes by Trojan antigens', Journal of Immunology, vol. 166, no. 12, pp. 7063-7071. https://doi.org/10.4049/jimmunol.166.12.7063
Lu, J. ; Wettstein, P. J. ; Higashimoto, Y. ; Appella, E. ; Celis, E. / TAP-independent presentation of CTL epitopes by Trojan antigens. In: Journal of Immunology. 2001 ; Vol. 166, No. 12. pp. 7063-7071.
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