Control of Self-Reactive Cytotoxic T Lymphocytes Expressing Gamma Delta T Cell Receptors by Natural Killer Inhibitory Receptors

Eur J Immunol. 1997 Nov;27(11):2812-21. doi: 10.1002/eji.1830271111.

Abstract

The majority of peripheral blood gamma delta T cells in human adults expresses T cell receptors (TCR) with identical V regions (V gamma 9 and V delta 2). These V gamma 9 V delta 2 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 alpha beta or V gamma 9- gamma delta T cells, the majority of V gamma 9V delta 2 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 V gamma 9V delta 2 T cells, KIR were mainly expressed by clones exhibiting a strong lytic activity against Daudi cells. In stark contrast, almost all V gamma 9V delta 2 T cell clones devoid of killing activity were KIR-, thus suggesting a coordinate acquisition of KIR and cytotoxic activity within V gamma 9V delta 2 T cells. In functional terms, KIR inhibited lysis of MHC class I-positive tumor B cell lines by V gamma 9V delta 2 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 V gamma 9V delta 2 CTL of ligands expressed by activated T lymphocytes, including the effector cells themselves. Taken together, these results suggest a general implication of V gamma 9V delta 2 T cells in immune response regulation and a central role of KIR in the control of self-reactive gamma delta CTL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Burkitt Lymphoma
  • Clone Cells
  • Cytotoxicity, Immunologic* / drug effects
  • HLA Antigens / physiology
  • Histocompatibility Antigens Class I / physiology
  • Humans
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism*
  • Leukemia, Erythroblastic, Acute
  • Lymphocyte Activation / drug effects
  • Lymphocyte Count
  • Multiple Myeloma
  • Receptors, Antigen, T-Cell, gamma-delta / biosynthesis*
  • Receptors, Antigen, T-Cell, gamma-delta / physiology
  • Receptors, Immunologic / biosynthesis
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / physiology*
  • Receptors, KIR
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism*
  • Tumor Cells, Cultured

Substances

  • HLA Antigens
  • Histocompatibility Antigens Class I
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Immunologic
  • Receptors, KIR