Induction of specific T-helper and cytolytic responses to epitopes displayed on a virus-like protein scaffold derived from the pyruvate dehydrogenase multienzyme complex

Gonzalo J. Domingo, Antonella Caivano, Rossella Sartorius, Pasquale Barba, Malin Bäckström, Dominique Piatier-Tonneau, John Guardiola, Piergiuseppe De Berardinis, Richard N. Perham

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The icosahedral protein scaffold (1.5MDa) generated by self-assembly of the catalytic domains of the dihydrolipoyl acetyltransferase core of the pyruvate dehydrogenase multienzyme complex from Bacillus stearothermophilus has been engineered to display 60 copies of one or more peptide epitopes on a single molecule (E2DISP). An E2DISP scaffold displaying pep23, a 15-residue B- and T-helper epitope from the reverse transcriptase of HIV-1, was able to induce a pep23-specific T-helper response in cell lines in vitro. The same scaffold displaying both pep23 and peptide RT2, a nine-residue CTL epitope from HIV-1 reverse transcriptase, was able to prime an RT2-specific CD8+ T-cell response in human cell lines in vitro and in HLA-A2 transgenic mice in vivo. This was accompanied by a humoral antibody response specific for E2DISP-presented epitopes. Thus, the icosahedral acetyltransferase core constitutes a simple and flexible scaffold for multiple epitope display with access to both cellular and humoral immune response pathways.

Original languageEnglish
Pages (from-to)1502-1509
Number of pages8
JournalVaccine
Volume21
Issue number13-14
DOIs
Publication statusPublished - Mar 28 2003

Fingerprint

pyruvate dehydrogenase (lipoamide)
multienzyme complexes
Multienzyme Complexes
scaffolding proteins
Pyruvate Dehydrogenase Complex
epitopes
Epitopes
Viruses
viruses
acetyltransferases
RNA-directed DNA polymerase
Human immunodeficiency virus 1
Proteins
Dihydrolipoyllysine-Residue Acetyltransferase
peptides
HLA-A2 Antigen
Geobacillus stearothermophilus
Cell Line
Peptides
Acetyltransferases

Keywords

  • Antigen presentation
  • CTL response
  • Dihydrolipoyl acetyltransferase

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Virology
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)

Cite this

Induction of specific T-helper and cytolytic responses to epitopes displayed on a virus-like protein scaffold derived from the pyruvate dehydrogenase multienzyme complex. / Domingo, Gonzalo J.; Caivano, Antonella; Sartorius, Rossella; Barba, Pasquale; Bäckström, Malin; Piatier-Tonneau, Dominique; Guardiola, John; De Berardinis, Piergiuseppe; Perham, Richard N.

In: Vaccine, Vol. 21, No. 13-14, 28.03.2003, p. 1502-1509.

Research output: Contribution to journalArticle

Domingo, GJ, Caivano, A, Sartorius, R, Barba, P, Bäckström, M, Piatier-Tonneau, D, Guardiola, J, De Berardinis, P & Perham, RN 2003, 'Induction of specific T-helper and cytolytic responses to epitopes displayed on a virus-like protein scaffold derived from the pyruvate dehydrogenase multienzyme complex', Vaccine, vol. 21, no. 13-14, pp. 1502-1509. https://doi.org/10.1016/S0264-410X(02)00664-3
Domingo, Gonzalo J. ; Caivano, Antonella ; Sartorius, Rossella ; Barba, Pasquale ; Bäckström, Malin ; Piatier-Tonneau, Dominique ; Guardiola, John ; De Berardinis, Piergiuseppe ; Perham, Richard N. / Induction of specific T-helper and cytolytic responses to epitopes displayed on a virus-like protein scaffold derived from the pyruvate dehydrogenase multienzyme complex. In: Vaccine. 2003 ; Vol. 21, No. 13-14. pp. 1502-1509.
@article{8694fa5e86a543a4ac81ecdfe0173d58,
title = "Induction of specific T-helper and cytolytic responses to epitopes displayed on a virus-like protein scaffold derived from the pyruvate dehydrogenase multienzyme complex",
abstract = "The icosahedral protein scaffold (1.5MDa) generated by self-assembly of the catalytic domains of the dihydrolipoyl acetyltransferase core of the pyruvate dehydrogenase multienzyme complex from Bacillus stearothermophilus has been engineered to display 60 copies of one or more peptide epitopes on a single molecule (E2DISP). An E2DISP scaffold displaying pep23, a 15-residue B- and T-helper epitope from the reverse transcriptase of HIV-1, was able to induce a pep23-specific T-helper response in cell lines in vitro. The same scaffold displaying both pep23 and peptide RT2, a nine-residue CTL epitope from HIV-1 reverse transcriptase, was able to prime an RT2-specific CD8+ T-cell response in human cell lines in vitro and in HLA-A2 transgenic mice in vivo. This was accompanied by a humoral antibody response specific for E2DISP-presented epitopes. Thus, the icosahedral acetyltransferase core constitutes a simple and flexible scaffold for multiple epitope display with access to both cellular and humoral immune response pathways.",
keywords = "Antigen presentation, CTL response, Dihydrolipoyl acetyltransferase",
author = "Domingo, {Gonzalo J.} and Antonella Caivano and Rossella Sartorius and Pasquale Barba and Malin B{\"a}ckstr{\"o}m and Dominique Piatier-Tonneau and John Guardiola and {De Berardinis}, Piergiuseppe and Perham, {Richard N.}",
year = "2003",
month = "3",
day = "28",
doi = "10.1016/S0264-410X(02)00664-3",
language = "English",
volume = "21",
pages = "1502--1509",
journal = "Vaccine",
issn = "0264-410X",
publisher = "Elsevier BV",
number = "13-14",

}

TY - JOUR

T1 - Induction of specific T-helper and cytolytic responses to epitopes displayed on a virus-like protein scaffold derived from the pyruvate dehydrogenase multienzyme complex

AU - Domingo, Gonzalo J.

AU - Caivano, Antonella

AU - Sartorius, Rossella

AU - Barba, Pasquale

AU - Bäckström, Malin

AU - Piatier-Tonneau, Dominique

AU - Guardiola, John

AU - De Berardinis, Piergiuseppe

AU - Perham, Richard N.

PY - 2003/3/28

Y1 - 2003/3/28

N2 - The icosahedral protein scaffold (1.5MDa) generated by self-assembly of the catalytic domains of the dihydrolipoyl acetyltransferase core of the pyruvate dehydrogenase multienzyme complex from Bacillus stearothermophilus has been engineered to display 60 copies of one or more peptide epitopes on a single molecule (E2DISP). An E2DISP scaffold displaying pep23, a 15-residue B- and T-helper epitope from the reverse transcriptase of HIV-1, was able to induce a pep23-specific T-helper response in cell lines in vitro. The same scaffold displaying both pep23 and peptide RT2, a nine-residue CTL epitope from HIV-1 reverse transcriptase, was able to prime an RT2-specific CD8+ T-cell response in human cell lines in vitro and in HLA-A2 transgenic mice in vivo. This was accompanied by a humoral antibody response specific for E2DISP-presented epitopes. Thus, the icosahedral acetyltransferase core constitutes a simple and flexible scaffold for multiple epitope display with access to both cellular and humoral immune response pathways.

AB - The icosahedral protein scaffold (1.5MDa) generated by self-assembly of the catalytic domains of the dihydrolipoyl acetyltransferase core of the pyruvate dehydrogenase multienzyme complex from Bacillus stearothermophilus has been engineered to display 60 copies of one or more peptide epitopes on a single molecule (E2DISP). An E2DISP scaffold displaying pep23, a 15-residue B- and T-helper epitope from the reverse transcriptase of HIV-1, was able to induce a pep23-specific T-helper response in cell lines in vitro. The same scaffold displaying both pep23 and peptide RT2, a nine-residue CTL epitope from HIV-1 reverse transcriptase, was able to prime an RT2-specific CD8+ T-cell response in human cell lines in vitro and in HLA-A2 transgenic mice in vivo. This was accompanied by a humoral antibody response specific for E2DISP-presented epitopes. Thus, the icosahedral acetyltransferase core constitutes a simple and flexible scaffold for multiple epitope display with access to both cellular and humoral immune response pathways.

KW - Antigen presentation

KW - CTL response

KW - Dihydrolipoyl acetyltransferase

UR - http://www.scopus.com/inward/record.url?scp=0037471414&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037471414&partnerID=8YFLogxK

U2 - 10.1016/S0264-410X(02)00664-3

DO - 10.1016/S0264-410X(02)00664-3

M3 - Article

C2 - 12615447

AN - SCOPUS:0037471414

VL - 21

SP - 1502

EP - 1509

JO - Vaccine

JF - Vaccine

SN - 0264-410X

IS - 13-14

ER -