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A common inhibitory receptor for major histocompatibility complex class I molecules on human lymphoid and myelomonocytic cells.

Colonna M, Navarro F, Bellón T, Llano M, García P, Samaridis J, Angman L, Cella M, López-Botet M - J. Exp. Med. (1997)

Bottom Line: In this study, we characterize a novel inhibitory MHC class I receptor of the immunoglobulin-superfamily, expressed not only by subsets of NK and T cells, but also by B cells, monocytes, macrophages, and dendritic cells.This receptor, called Ig-like transcript (ILT)2, binds MHC class I molecules and delivers a negative signal that inhibits killing by NK and T cells, as well as Ca2+ mobilization in B cells and myelomonocytic cells triggered through the B cell antigen receptor and human histocompatibility leukocyte antigens (HLA)-DR, respectively.In addition, myelomonocytic cells express receptors homologous to ILT2, which are characterized by extensive polymorphism and might recognize distinct HLA class I molecules.

View Article: PubMed Central - PubMed

Affiliation: Basel Institute for Immunology, Basel CH-4005, Switzerland.

ABSTRACT
Natural killer (NK) cell-mediated lysis is negatively regulated by killer cell inhibitory receptors specific for major histocompatibility complex (MHC) class I molecules. In this study, we characterize a novel inhibitory MHC class I receptor of the immunoglobulin-superfamily, expressed not only by subsets of NK and T cells, but also by B cells, monocytes, macrophages, and dendritic cells. This receptor, called Ig-like transcript (ILT)2, binds MHC class I molecules and delivers a negative signal that inhibits killing by NK and T cells, as well as Ca2+ mobilization in B cells and myelomonocytic cells triggered through the B cell antigen receptor and human histocompatibility leukocyte antigens (HLA)-DR, respectively. In addition, myelomonocytic cells express receptors homologous to ILT2, which are characterized by extensive polymorphism and might recognize distinct HLA class I molecules. These results suggest that diverse leukocyte lineages have adopted recognition of self-MHC class I molecules as a common strategy to control cellular activation during an immune response.

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ILT2-class I interaction inhibits TSST-1–mediated T cell cytotoxicity. HP-F1+ T cell clones were generated from the peripheral  blood of a healthy donor and selected for expression of TCR-Vβ2 and  for lack of KIR expression. T cell clones were then tested in a 4-h 51Cr-release assay for cytotoxicity against the class I–negative B lymphoblastoid  cell line 721.221 cells or 721.221 cells stably transfected with HLA-B*2705, in the presence of serial dilutions of TSST-1 at an effector/target  ratio of 20:1. The T cell clone OKT8-24 killed 721.221 in the presence  of TSST-1, but did not kill B*2705-transfected cells. F(ab′)2 fragments of  the HP-F1 mAb partially restored the lysis, while F(ab′)2 fragments of the  isotype-matched anti-CD56 mAb had no effect.
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Figure 7: ILT2-class I interaction inhibits TSST-1–mediated T cell cytotoxicity. HP-F1+ T cell clones were generated from the peripheral blood of a healthy donor and selected for expression of TCR-Vβ2 and for lack of KIR expression. T cell clones were then tested in a 4-h 51Cr-release assay for cytotoxicity against the class I–negative B lymphoblastoid cell line 721.221 cells or 721.221 cells stably transfected with HLA-B*2705, in the presence of serial dilutions of TSST-1 at an effector/target ratio of 20:1. The T cell clone OKT8-24 killed 721.221 in the presence of TSST-1, but did not kill B*2705-transfected cells. F(ab′)2 fragments of the HP-F1 mAb partially restored the lysis, while F(ab′)2 fragments of the isotype-matched anti-CD56 mAb had no effect.

Mentions: We next tested whether ILT2 mediates functional inhibition in cell types other than NK cells. CD8+ T cells kill MHC class II+ APCs pulsed with bacterial superantigens, which bind the variable region of the TCR-β chain (Vβ) on T cells. We investigated whether this superantigen-dependent cell-mediated cytotoxicity is inhibited by interaction between ILT2 on T cells and class I on APCs. HP-F1+ T cells were sorted and cloned; T cell clones were then selected for expression of Vβ2, which binds the toxic shock syndrome toxin–1 (TSST-1) superantigen, and for lack of KIR expression. T cell–mediated cytotoxicity was tested against either 721.221 cells or an HLA-B*2705 transfectant of 721.221 pulsed with different concentrations of TSST-1. Both target cells expressed equivalent levels of MHC class II molecules. Results from a representative clone are shown in Fig. 7. The OKT8-24 T cell clone efficiently killed TSST-1–coated 721.221, whereas cytolytic activity was significantly reduced against TSST-1–pulsed HLA-B*2705 transfectants. Cytolysis of TSST-1–coated HLA-B*2705 transfectants was partially reconstituted in the presence of F(ab′)2 fragments of the HP-F1 mAb. These results indicate that ILT2–class I interaction, like KIR–class I interaction, inhibits superantigen-dependent T cell–mediated cytotoxicity and may explain previous reports of KIR− T cells inhibited by HLA-B27 molecules (38).


A common inhibitory receptor for major histocompatibility complex class I molecules on human lymphoid and myelomonocytic cells.

Colonna M, Navarro F, Bellón T, Llano M, García P, Samaridis J, Angman L, Cella M, López-Botet M - J. Exp. Med. (1997)

ILT2-class I interaction inhibits TSST-1–mediated T cell cytotoxicity. HP-F1+ T cell clones were generated from the peripheral  blood of a healthy donor and selected for expression of TCR-Vβ2 and  for lack of KIR expression. T cell clones were then tested in a 4-h 51Cr-release assay for cytotoxicity against the class I–negative B lymphoblastoid  cell line 721.221 cells or 721.221 cells stably transfected with HLA-B*2705, in the presence of serial dilutions of TSST-1 at an effector/target  ratio of 20:1. The T cell clone OKT8-24 killed 721.221 in the presence  of TSST-1, but did not kill B*2705-transfected cells. F(ab′)2 fragments of  the HP-F1 mAb partially restored the lysis, while F(ab′)2 fragments of the  isotype-matched anti-CD56 mAb had no effect.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2199153&req=5

Figure 7: ILT2-class I interaction inhibits TSST-1–mediated T cell cytotoxicity. HP-F1+ T cell clones were generated from the peripheral blood of a healthy donor and selected for expression of TCR-Vβ2 and for lack of KIR expression. T cell clones were then tested in a 4-h 51Cr-release assay for cytotoxicity against the class I–negative B lymphoblastoid cell line 721.221 cells or 721.221 cells stably transfected with HLA-B*2705, in the presence of serial dilutions of TSST-1 at an effector/target ratio of 20:1. The T cell clone OKT8-24 killed 721.221 in the presence of TSST-1, but did not kill B*2705-transfected cells. F(ab′)2 fragments of the HP-F1 mAb partially restored the lysis, while F(ab′)2 fragments of the isotype-matched anti-CD56 mAb had no effect.
Mentions: We next tested whether ILT2 mediates functional inhibition in cell types other than NK cells. CD8+ T cells kill MHC class II+ APCs pulsed with bacterial superantigens, which bind the variable region of the TCR-β chain (Vβ) on T cells. We investigated whether this superantigen-dependent cell-mediated cytotoxicity is inhibited by interaction between ILT2 on T cells and class I on APCs. HP-F1+ T cells were sorted and cloned; T cell clones were then selected for expression of Vβ2, which binds the toxic shock syndrome toxin–1 (TSST-1) superantigen, and for lack of KIR expression. T cell–mediated cytotoxicity was tested against either 721.221 cells or an HLA-B*2705 transfectant of 721.221 pulsed with different concentrations of TSST-1. Both target cells expressed equivalent levels of MHC class II molecules. Results from a representative clone are shown in Fig. 7. The OKT8-24 T cell clone efficiently killed TSST-1–coated 721.221, whereas cytolytic activity was significantly reduced against TSST-1–pulsed HLA-B*2705 transfectants. Cytolysis of TSST-1–coated HLA-B*2705 transfectants was partially reconstituted in the presence of F(ab′)2 fragments of the HP-F1 mAb. These results indicate that ILT2–class I interaction, like KIR–class I interaction, inhibits superantigen-dependent T cell–mediated cytotoxicity and may explain previous reports of KIR− T cells inhibited by HLA-B27 molecules (38).

Bottom Line: In this study, we characterize a novel inhibitory MHC class I receptor of the immunoglobulin-superfamily, expressed not only by subsets of NK and T cells, but also by B cells, monocytes, macrophages, and dendritic cells.This receptor, called Ig-like transcript (ILT)2, binds MHC class I molecules and delivers a negative signal that inhibits killing by NK and T cells, as well as Ca2+ mobilization in B cells and myelomonocytic cells triggered through the B cell antigen receptor and human histocompatibility leukocyte antigens (HLA)-DR, respectively.In addition, myelomonocytic cells express receptors homologous to ILT2, which are characterized by extensive polymorphism and might recognize distinct HLA class I molecules.

View Article: PubMed Central - PubMed

Affiliation: Basel Institute for Immunology, Basel CH-4005, Switzerland.

ABSTRACT
Natural killer (NK) cell-mediated lysis is negatively regulated by killer cell inhibitory receptors specific for major histocompatibility complex (MHC) class I molecules. In this study, we characterize a novel inhibitory MHC class I receptor of the immunoglobulin-superfamily, expressed not only by subsets of NK and T cells, but also by B cells, monocytes, macrophages, and dendritic cells. This receptor, called Ig-like transcript (ILT)2, binds MHC class I molecules and delivers a negative signal that inhibits killing by NK and T cells, as well as Ca2+ mobilization in B cells and myelomonocytic cells triggered through the B cell antigen receptor and human histocompatibility leukocyte antigens (HLA)-DR, respectively. In addition, myelomonocytic cells express receptors homologous to ILT2, which are characterized by extensive polymorphism and might recognize distinct HLA class I molecules. These results suggest that diverse leukocyte lineages have adopted recognition of self-MHC class I molecules as a common strategy to control cellular activation during an immune response.

Show MeSH
Related in: MedlinePlus