Identification of effector-memory CMV-specific T lymphocytes that kill CMV-infected target cells in an HLA-E-restricted fashion

Paola Mazzarino, Gabriella Pietra, Paola Vacca, Michela Falco, Didier Colau, Pierre Coulie, Lorenzo Moretta, Maria Cristina Mingari

Research output: Contribution to journalArticlepeer-review

Abstract

HLA-E-restricted T cells represent a minor cytolytic T lymphocyte (CTL) population characterized by the surface expression of HLA class I-specific inhibitory receptors and by the capability of killing a large panel of allogeneic target cells (therefore named NK-CTL). Here we show that this subset of T cells is present in a sizeable fraction in the peripheral blood of human cytomegalovirus (HCMV)-seropositive healthy individuals. We provide evidence that NK-CTL recognize in an HLA-E-restricted fashion a naturally processed CMV-derived peptide in the transporter associated with antigen processing (TAP)-2-/- UL40+ RMA-S cell transfectants. Moreover, we show that they recognize and kill HCMV-infected target cells. NK-CTL are characterized by the CD8βdull CD45RA+CD28- CD27-CCR7-CD56+ surface phenotype, thus suggesting that they belong to the effector-memory cell compartment. Consistent with the effector-memory phenotype, they promptly produce IFN-γ, but not IL-2, upon interaction with the specific HCMV UL40-derived peptide. Our data suggest that HLA-E-restricted CTL may represent an additional effector cell type involved in defenses against HCMV, a virus which escapes the control exerted by conventional CTL or NK cells.

Original languageEnglish
Pages (from-to)3240-3247
Number of pages8
JournalEuropean Journal of Immunology
Volume35
Issue number11
DOIs
Publication statusPublished - Nov 2005

Keywords

  • Effector-memory T cells
  • HLA-E
  • Human CMV
  • NK-CTL

ASJC Scopus subject areas

  • Immunology

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