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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-F1 antigen is expressed on CD56+ NK cells (23– 77% in six different donors), α/β T cells (3–28%), γ/δ T cells (16–50%),  CD19+ B cells, CD14+ monocytes, HLA-DRhigh DCs derived from  CD34+ precursors, and CD1a+ DCs derived from monocytes under appropriate culture conditions. Macrophages derived in vitro from purified  monocytes also expressed the HP-F1 antigen, whereas neutrophils were  HP-F1− (data not shown).
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Figure 2: The HP-F1 antigen is expressed on CD56+ NK cells (23– 77% in six different donors), α/β T cells (3–28%), γ/δ T cells (16–50%), CD19+ B cells, CD14+ monocytes, HLA-DRhigh DCs derived from CD34+ precursors, and CD1a+ DCs derived from monocytes under appropriate culture conditions. Macrophages derived in vitro from purified monocytes also expressed the HP-F1 antigen, whereas neutrophils were HP-F1− (data not shown).

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-F1 antigen is expressed on CD56+ NK cells (23– 77% in six different donors), α/β T cells (3–28%), γ/δ T cells (16–50%),  CD19+ B cells, CD14+ monocytes, HLA-DRhigh DCs derived from  CD34+ precursors, and CD1a+ DCs derived from monocytes under appropriate culture conditions. Macrophages derived in vitro from purified  monocytes also expressed the HP-F1 antigen, whereas neutrophils were  HP-F1− (data not shown).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: The HP-F1 antigen is expressed on CD56+ NK cells (23– 77% in six different donors), α/β T cells (3–28%), γ/δ T cells (16–50%), CD19+ B cells, CD14+ monocytes, HLA-DRhigh DCs derived from CD34+ precursors, and CD1a+ DCs derived from monocytes under appropriate culture conditions. Macrophages derived in vitro from purified monocytes also expressed the HP-F1 antigen, whereas neutrophils were HP-F1− (data not shown).
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