TY - JOUR
T1 - Control of self-reactive cytotoxic T lymphocytes expressing γδ T cell receptors by natural killer inhibitory receptors
AU - Halary, Franck
AU - Peyrat, Marie Alix
AU - Champagne, Eric
AU - Lopez-Botet, Miguel
AU - Moretta, Alessandro
AU - Moretta, Lorenzo
AU - Vié, Henri
AU - Fournié, Jean Jacques
AU - Bonneville, Marc
PY - 1997/11
Y1 - 1997/11
N2 - 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.
AB - 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.
KW - γδ T cell receptor
KW - Cytotoxicity
KW - Natural killer receptor
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U2 - 10.1002/eji.1830271111
DO - 10.1002/eji.1830271111
M3 - Article
C2 - 9394804
AN - SCOPUS:0030702062
VL - 27
SP - 2812
EP - 2821
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 11
ER -