The matrix protein pp65341-350: A peptide that induces ex vivo stimulation and in vitro expansion of CMV-specific CD8+ T cells in subjects bearing either HLA-A*2402 or A*0101 allele

Maurizio Provenzano, Jong Baeck Lim, Simone Mocellin, Vladia Monsurro, Maria Bettinotti, Francesco M. Marincola, David F. Stroncek

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: The stimulation of PBMNCs with HLA Class I restricted synthetic peptides derived from CMV phosphorylated matrix protein 65 (pp65) evokes CMV-specific cytotoxic T lymphocyte (CTL) activity, a necessary condition for initiating adoptive immunotherapy against CMV-related diseases in immune-compromised patients. It was previously demonstrated that the CMV decamer (10-mer) peptide pp65341-350, QYDPVAALFF, was able to induce CMV-specific CTLs in HLA-A*2402 CMV-seropositive individuals. STUDY DESIGN AND METHOD: We investigated the ability of the peptide pp65 341-350 to reactivate memory CD8+ T cells in CMV-seropositive subjects bearing either the HLA-A24 or A1 allele. CTL responses were measured by IFN-γ mRNA expression and IFN-γ protein production as well as cytotoxic activity. RESULTS: In this study it was found that peptide pp65 341-350 induced a specific reactivation of memory CD8+ T cells from CMV-seropositive donors expressing either HLA-A*2402 and/or HLA-A*0101. Moreover, a pp65341-350-specific selection and expansion using PBMNCs of CMV-seropositive donors bearing both HLA-A*2402 and HLA-A*0101 alleles produced cytotoxic CTLs to both HLA-A24 and A1 peptide-pulsed and autologous CMV-infected target cells. CONCLUSION: The results demonstrate that pp65341-350 induced a specific CTL activity at both molecular and protein levels and that the peptide is specifically processed, presented, and recognized by subjects bearing HLA-A*2402 and/ or A*0101. These findings suggest that it may be possible to use this single immune dominant peptide to induce and expand CMV-reactive CTLs for the treatment of individuals with both HLA-A24 and A1 types.

Original languageEnglish (US)
Pages (from-to)1567-1574
Number of pages8
JournalTransfusion
Volume43
Issue number11
DOIs
StatePublished - Nov 2003
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

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