Activation of epitope-specific memory cytotoxic T lymphocyte responses by synthetic peptides

E. Reali, R. Guerrini, B. Giori, M. Borghi, M. Marastoni, R. Tomatis, S. Traniello, M. G. Masucci, R. Gavioli

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Cytotoxic T lymphocytes (CTL) recognize antigens as short peptides selected for presentation by their ability to bind to MHC class I molecules. Polyclonal Epstein-Barr virus (EBV)-specific memory CTL responses, reactivated from blood lymphocytes of HLA-A11-positive individuals by stimulation with the autologous EBV-transformed lymphoblastoid cell line (LCL), are often dominated by reactivities directed to the peptide epitope IVTDFSVIK (IVT), corresponding to amino acids 416-424 of EBV nuclear antigen-4 (EBNA4). We now report the selective activation of IVT-specific CTL by stimulation of lymphocytes with the corresponding synthetic peptide. A more than 10-fold increase in frequency of CTL clones with this specificity (from 8% to 96%) was obtained when the peptide was presented by HLA-A11-transfected T2 cells (T2/A11). Titration of synthetic peptide in cytotoxic assay demonstrated that clones activated under these conditions are as efficient as clones activated by conventional LCL stimulations. Induction of memory CTL responses required low surface density of MHC:peptide complexes, since reactivation was achieved by stimulation with T2/A11 cells pulsed with concentrations of peptide that are suboptimal for induction of target cell lysis. This protocol of activation revealed the presence of IVT-specific CTL precursors in a donor that failed to mount an IVT-specific response upon stimulation with the autologous B95.8 virus-transformed LCL. The results suggest that stimulation with synthetic peptide epitopes can be efficiently used for induction of memory CTL responses, and may be particularly helpful for the selective expansion of subdominant CTL specificities.

Original languageEnglish
Pages (from-to)369-375
Number of pages7
JournalClinical and Experimental Immunology
Volume105
Issue number2
Publication statusPublished - 1996

Fingerprint

Cytotoxic T-Lymphocytes
Epitopes
Peptides
HLA-A11 Antigen
Transformed Cell Line
Clone Cells
Human Herpesvirus 4
Epstein-Barr Virus Nuclear Antigens
Lymphocytes
Aptitude
Lymphocyte Activation
Viruses
Antigens
Amino Acids
Cell Line

Keywords

  • Cytotoxic T lymphocytes
  • Epstein-Barr virus
  • HLA-A11
  • Immunogenic peptides

ASJC Scopus subject areas

  • Immunology

Cite this

Reali, E., Guerrini, R., Giori, B., Borghi, M., Marastoni, M., Tomatis, R., ... Gavioli, R. (1996). Activation of epitope-specific memory cytotoxic T lymphocyte responses by synthetic peptides. Clinical and Experimental Immunology, 105(2), 369-375.

Activation of epitope-specific memory cytotoxic T lymphocyte responses by synthetic peptides. / Reali, E.; Guerrini, R.; Giori, B.; Borghi, M.; Marastoni, M.; Tomatis, R.; Traniello, S.; Masucci, M. G.; Gavioli, R.

In: Clinical and Experimental Immunology, Vol. 105, No. 2, 1996, p. 369-375.

Research output: Contribution to journalArticle

Reali, E, Guerrini, R, Giori, B, Borghi, M, Marastoni, M, Tomatis, R, Traniello, S, Masucci, MG & Gavioli, R 1996, 'Activation of epitope-specific memory cytotoxic T lymphocyte responses by synthetic peptides', Clinical and Experimental Immunology, vol. 105, no. 2, pp. 369-375.
Reali E, Guerrini R, Giori B, Borghi M, Marastoni M, Tomatis R et al. Activation of epitope-specific memory cytotoxic T lymphocyte responses by synthetic peptides. Clinical and Experimental Immunology. 1996;105(2):369-375.
Reali, E. ; Guerrini, R. ; Giori, B. ; Borghi, M. ; Marastoni, M. ; Tomatis, R. ; Traniello, S. ; Masucci, M. G. ; Gavioli, R. / Activation of epitope-specific memory cytotoxic T lymphocyte responses by synthetic peptides. In: Clinical and Experimental Immunology. 1996 ; Vol. 105, No. 2. pp. 369-375.
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