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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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The HP-F1γ receptor is an ∼110-kD monomeric  glycoprotein. (Left) Immunoprecipitation from 125I-labeled  NKL cells with HP-F1 mAb  yields a protein which runs as a  110-kD band in SDS-PAGE under reducing conditions. After  treatment with N-glycosidase,  the molecular mass is reduced to  ∼90 kD. (Right) Identical electrophoretic patterns were obtained by SDS-PAGE analysis of  immunoprecipitates from ILT2-transfected COS7 cells. No  bands were detected using the culture supernatant from X63 murine myeloma in control experiments.
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Figure 3: The HP-F1γ receptor is an ∼110-kD monomeric glycoprotein. (Left) Immunoprecipitation from 125I-labeled NKL cells with HP-F1 mAb yields a protein which runs as a 110-kD band in SDS-PAGE under reducing conditions. After treatment with N-glycosidase, the molecular mass is reduced to ∼90 kD. (Right) Identical electrophoretic patterns were obtained by SDS-PAGE analysis of immunoprecipitates from ILT2-transfected COS7 cells. No bands were detected using the culture supernatant from X63 murine myeloma in control experiments.

Mentions: In PBMCs, the HP-F1 antigen was detected not only on a fraction of NK cells, α/β and γ/δ T cells (as previously observed for KIRs) but, strikingly, also on almost all CD19+ B cells and CD14+ monocytes (Fig. 2). In addition, the HP-F1 mAb stained HLA-DRhigh DCs derived from CD34+ hematopoietic precursors, as well as DCs and macrophages derived from purified monocytes under appropriate culture conditions (Fig. 2 and data not shown). In immunoprecipitation experiments from different cell types, the HP-F1 mAb detected a prominent band of ∼110 kD under both nonreducing (not shown) and reducing conditions, and of ∼90 kD after N-deglycosylation of the immunoprecipitates (Fig. 3, left). Its cellular distribution along with biochemical analyses indicated that the HP-F1 antigen differs from previously identified KIRs but is similar to a recently cloned candidate inhibitory receptor, termed ILT2 (13). The predicted ILT2 glycoprotein is characterized by an extracellular region of four Ig-SF domains and a cytoplasmic tail containing four tyrosine-based motifs similar to the ITIMs of KIRs that recruit SHP-1 phosphatase upon phosphorylation (29–33). Specific staining (not shown) and immunoprecipitation (Fig. 3, right) of ILT2-transfected COS cells with the HP-F1 mAb demonstrated that the HP-F1 antigen does indeed correspond to the ILT2-encoded glycoprotein.


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)

The HP-F1γ receptor is an ∼110-kD monomeric  glycoprotein. (Left) Immunoprecipitation from 125I-labeled  NKL cells with HP-F1 mAb  yields a protein which runs as a  110-kD band in SDS-PAGE under reducing conditions. After  treatment with N-glycosidase,  the molecular mass is reduced to  ∼90 kD. (Right) Identical electrophoretic patterns were obtained by SDS-PAGE analysis of  immunoprecipitates from ILT2-transfected COS7 cells. No  bands were detected using the culture supernatant from X63 murine myeloma in control experiments.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: The HP-F1γ receptor is an ∼110-kD monomeric glycoprotein. (Left) Immunoprecipitation from 125I-labeled NKL cells with HP-F1 mAb yields a protein which runs as a 110-kD band in SDS-PAGE under reducing conditions. After treatment with N-glycosidase, the molecular mass is reduced to ∼90 kD. (Right) Identical electrophoretic patterns were obtained by SDS-PAGE analysis of immunoprecipitates from ILT2-transfected COS7 cells. No bands were detected using the culture supernatant from X63 murine myeloma in control experiments.
Mentions: In PBMCs, the HP-F1 antigen was detected not only on a fraction of NK cells, α/β and γ/δ T cells (as previously observed for KIRs) but, strikingly, also on almost all CD19+ B cells and CD14+ monocytes (Fig. 2). In addition, the HP-F1 mAb stained HLA-DRhigh DCs derived from CD34+ hematopoietic precursors, as well as DCs and macrophages derived from purified monocytes under appropriate culture conditions (Fig. 2 and data not shown). In immunoprecipitation experiments from different cell types, the HP-F1 mAb detected a prominent band of ∼110 kD under both nonreducing (not shown) and reducing conditions, and of ∼90 kD after N-deglycosylation of the immunoprecipitates (Fig. 3, left). Its cellular distribution along with biochemical analyses indicated that the HP-F1 antigen differs from previously identified KIRs but is similar to a recently cloned candidate inhibitory receptor, termed ILT2 (13). The predicted ILT2 glycoprotein is characterized by an extracellular region of four Ig-SF domains and a cytoplasmic tail containing four tyrosine-based motifs similar to the ITIMs of KIRs that recruit SHP-1 phosphatase upon phosphorylation (29–33). Specific staining (not shown) and immunoprecipitation (Fig. 3, right) of ILT2-transfected COS cells with the HP-F1 mAb demonstrated that the HP-F1 antigen does indeed correspond to the ILT2-encoded glycoprotein.

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