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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 soluble protein binds HLA-A, -B, and -G1 transfectants. HLA-B*2702, -B*2705, -A*0301, -G1, and -Cw*0301 transfectants  in 721.221 and untransfected cells were incubated with a soluble ILT2– IgG1 fusion protein, followed by a PE-labeled goat anti–human IgG antibody. Binding was assessed by FACS® analysis. HLA class I expression of  the transfectants was determined in the same experiment by FACS® analysis using the w6/32 mAb (IgG2a; American Type Culture Collection).  MFI were as follows: 721.221, 121; HLA-B*2702, 2128; -B*2705, 3045;  -A*0301, 3854; -G1, 1084; -Cw*0301, 1582. The binding pattern did not  correlate with the level of class I expression on the transfectants.
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Figure 4: ILT2 soluble protein binds HLA-A, -B, and -G1 transfectants. HLA-B*2702, -B*2705, -A*0301, -G1, and -Cw*0301 transfectants in 721.221 and untransfected cells were incubated with a soluble ILT2– IgG1 fusion protein, followed by a PE-labeled goat anti–human IgG antibody. Binding was assessed by FACS® analysis. HLA class I expression of the transfectants was determined in the same experiment by FACS® analysis using the w6/32 mAb (IgG2a; American Type Culture Collection). MFI were as follows: 721.221, 121; HLA-B*2702, 2128; -B*2705, 3045; -A*0301, 3854; -G1, 1084; -Cw*0301, 1582. The binding pattern did not correlate with the level of class I expression on the transfectants.

Mentions: To provide direct evidence that ILT2 is a receptor for HLA–class I molecules, we analyzed binding of a soluble ILT2–IgG1 fusion protein to class I transfectants in 721.221 by flow cytometry. HLA-B*2702, -B*2705, -A*0301, -G1, and -Cw*0301 transfectants and 721.221 cells were incubated with ILT2–IgG1 and stained with anti–human IgG antibody. As shown in Fig. 4, ILT2 bound HLA-A, -B, and -G1 transfectants but not HLA-Cw3 transfectants or 721.221 cells. These data provide formal demonstration that ILT2 is a receptor for HLA–class I molecules, apparently with a broad specificity.


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 soluble protein binds HLA-A, -B, and -G1 transfectants. HLA-B*2702, -B*2705, -A*0301, -G1, and -Cw*0301 transfectants  in 721.221 and untransfected cells were incubated with a soluble ILT2– IgG1 fusion protein, followed by a PE-labeled goat anti–human IgG antibody. Binding was assessed by FACS® analysis. HLA class I expression of  the transfectants was determined in the same experiment by FACS® analysis using the w6/32 mAb (IgG2a; American Type Culture Collection).  MFI were as follows: 721.221, 121; HLA-B*2702, 2128; -B*2705, 3045;  -A*0301, 3854; -G1, 1084; -Cw*0301, 1582. The binding pattern did not  correlate with the level of class I expression on the transfectants.
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Related In: Results  -  Collection

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Figure 4: ILT2 soluble protein binds HLA-A, -B, and -G1 transfectants. HLA-B*2702, -B*2705, -A*0301, -G1, and -Cw*0301 transfectants in 721.221 and untransfected cells were incubated with a soluble ILT2– IgG1 fusion protein, followed by a PE-labeled goat anti–human IgG antibody. Binding was assessed by FACS® analysis. HLA class I expression of the transfectants was determined in the same experiment by FACS® analysis using the w6/32 mAb (IgG2a; American Type Culture Collection). MFI were as follows: 721.221, 121; HLA-B*2702, 2128; -B*2705, 3045; -A*0301, 3854; -G1, 1084; -Cw*0301, 1582. The binding pattern did not correlate with the level of class I expression on the transfectants.
Mentions: To provide direct evidence that ILT2 is a receptor for HLA–class I molecules, we analyzed binding of a soluble ILT2–IgG1 fusion protein to class I transfectants in 721.221 by flow cytometry. HLA-B*2702, -B*2705, -A*0301, -G1, and -Cw*0301 transfectants and 721.221 cells were incubated with ILT2–IgG1 and stained with anti–human IgG antibody. As shown in Fig. 4, ILT2 bound HLA-A, -B, and -G1 transfectants but not HLA-Cw3 transfectants or 721.221 cells. These data provide formal demonstration that ILT2 is a receptor for HLA–class I molecules, apparently with a broad specificity.

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