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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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Intracellular Ca2+ mobilization induced by anti–human IgG antibodies in the EBV-B cell line C1R (a) is inhibited upon crosslinking with  ILT2 (b). Similarly, the increased [Ca2+]i triggered through HLA-DR by the 3.8 B1 mAb in monocytes (c) and dendritic cells (not shown) is downregulated, although to a lesser extent, when ILT2 is coligated with HLA-DR (d). HP-1F7 is an isotype-matched control antibody.
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Figure 8: Intracellular Ca2+ mobilization induced by anti–human IgG antibodies in the EBV-B cell line C1R (a) is inhibited upon crosslinking with ILT2 (b). Similarly, the increased [Ca2+]i triggered through HLA-DR by the 3.8 B1 mAb in monocytes (c) and dendritic cells (not shown) is downregulated, although to a lesser extent, when ILT2 is coligated with HLA-DR (d). HP-1F7 is an isotype-matched control antibody.

Mentions: To explore the regulatory role of ILT2 in B cell activation, we tested whether ILT2 can inhibit Ca2+ mobilization triggered via the B cell antigen receptor. Cocross-linking of ILT2 with surface IgG induced a complete extinction of the increased [Ca2+]i triggered through surface IgG in the EBV-transformed B cell line C1R (Fig. 8, a and b), while only a slight reduction was detected in peripheral B cells (data not shown). Since C1R has a very low level of class I expression, the HP-F1 mAb might be able to compete more effectively with self–class I molecules for binding with ILT2 and to recruit it to the B cell receptor in cross-linking experiments. Similarly, we obtained a moderate downregulation of Ca2+ mobilization triggered through HLA-DR in monocytes, macrophages, and DCs (Fig. 8, c and d, and data not shown). Together, these results demonstrate that ILT2 can modulate signaling in B cells and myelomonocytic cells. However, the physiological functions regulated by class I–ILT2 interactions in these cell types have yet to be defined.


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)

Intracellular Ca2+ mobilization induced by anti–human IgG antibodies in the EBV-B cell line C1R (a) is inhibited upon crosslinking with  ILT2 (b). Similarly, the increased [Ca2+]i triggered through HLA-DR by the 3.8 B1 mAb in monocytes (c) and dendritic cells (not shown) is downregulated, although to a lesser extent, when ILT2 is coligated with HLA-DR (d). HP-1F7 is an isotype-matched control antibody.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199153&req=5

Figure 8: Intracellular Ca2+ mobilization induced by anti–human IgG antibodies in the EBV-B cell line C1R (a) is inhibited upon crosslinking with ILT2 (b). Similarly, the increased [Ca2+]i triggered through HLA-DR by the 3.8 B1 mAb in monocytes (c) and dendritic cells (not shown) is downregulated, although to a lesser extent, when ILT2 is coligated with HLA-DR (d). HP-1F7 is an isotype-matched control antibody.
Mentions: To explore the regulatory role of ILT2 in B cell activation, we tested whether ILT2 can inhibit Ca2+ mobilization triggered via the B cell antigen receptor. Cocross-linking of ILT2 with surface IgG induced a complete extinction of the increased [Ca2+]i triggered through surface IgG in the EBV-transformed B cell line C1R (Fig. 8, a and b), while only a slight reduction was detected in peripheral B cells (data not shown). Since C1R has a very low level of class I expression, the HP-F1 mAb might be able to compete more effectively with self–class I molecules for binding with ILT2 and to recruit it to the B cell receptor in cross-linking experiments. Similarly, we obtained a moderate downregulation of Ca2+ mobilization triggered through HLA-DR in monocytes, macrophages, and DCs (Fig. 8, c and d, and data not shown). Together, these results demonstrate that ILT2 can modulate signaling in B cells and myelomonocytic cells. However, the physiological functions regulated by class I–ILT2 interactions in these cell types have yet to be defined.

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