Control of self-reactive cytotoxic T lymphocytes expressing γδ T cell receptors by natural killer inhibitory receptors

Franck Halary, Marie Alix Peyrat, Eric Champagne, Miguel Lopez-Botet, Alessandro Moretta, Lorenzo Moretta, Henri Vié, Jean Jacques Fournié, Marc Bonneville

Research output: Contribution to journalArticlepeer-review

Abstract

The majority of peripheral blood γδ T cells in human adults expresses T cell receptors (TCR) with identical V regions (Vγ9 and Vδ2). These Vγ9Vδ2 T cells recognize the major histocompatibility complex (MHC) class I-deficient B cell line Daudi and broadly distributed nonpeptidic antigens present in bacteria and parasites. Here we show that unlike αβ or Vγ9- γδ T cells. the majority of Vγ9Vδ2 T cells harbor natural killer inhibitory receptors (KIR) (mainly CD94/ NKG2A heterodimers), which are known to deliver inhibitory signals upon interaction with MHC class I molecules. Within Vγ9Vδ2 T cells, KIR were mainly expressed by clones exhibiting a strong lytic activity against Daudi cells. In stark contrast, almost all Vγ9Vδ2 T cell clones devoid of killing activity were KIR-, thus suggesting a coordinate acquisition of KIR and cytotoxic activity within Vγ9Vδ2 T cells. In functional terms, KIR inhibited lysis of MHC class I-positive tumor B cell lines by Vγ9Vδ2 cytotoxic T lymphocytes (CTL) and raised their threshold of activation by microbial antigens presented by MHC class I-positive cells. Furthermore, masking KIR or MHC class I molecules revealed a TCR-dependent recognition by Vγ9Vδ2 CTL of ligands expressed by activated T lymphocytes, including the effector cells themselves. Taken together, these results suggest a general implication of Vγ9Vδ2 T cells in immune response regulation and a central role of KIR in the control of self-reactive γδ CTL.

Original languageEnglish
Pages (from-to)2812-2821
Number of pages10
JournalEuropean Journal of Immunology
Volume27
Issue number11
DOIs
Publication statusPublished - Nov 1997

Keywords

  • γδ T cell receptor
  • Cytotoxicity
  • Natural killer receptor

ASJC Scopus subject areas

  • Immunology

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