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A novel inhibitory receptor (ILT3) expressed on monocytes, macrophages, and dendritic cells involved in antigen processing.

Cella M, Döhring C, Samaridis J, Dessing M, Brockhaus M, Lanzavecchia A, Colonna M - J. Exp. Med. (1997)

Bottom Line: Indeed, co-ligation of ILT3 to stimulatory receptors expressed by APCs results in a dramatic blunting of the increased [Ca2+]i and tyrosine phosphorylation triggered by these receptors.It is efficiently internalized upon cross-linking, and delivers its ligand to an intracellular compartment where it is processed and presented to T cells.Thus, ILT3 is a novel inhibitory receptor that can negatively regulate activation of APCs and can be used by APCs for antigen uptake.

View Article: PubMed Central - PubMed

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

ABSTRACT
Immunoglobulin-like transcript (ILT) 3 is a novel cell surface molecule of the immunoglobulin superfamily, which is selectively expressed by myeloid antigen presenting cells (APCs) such as monocytes, macrophages, and dendritic cells. The cytoplasmic region of ILT3 contains putative immunoreceptor tyrosine-based inhibitory motifs that suggest an inhibitory function of ILT3. Indeed, co-ligation of ILT3 to stimulatory receptors expressed by APCs results in a dramatic blunting of the increased [Ca2+]i and tyrosine phosphorylation triggered by these receptors. Signal extinction involves SH2-containing protein tyrosine phosphatase 1, which is recruited by ILT3 upon cross-linking. ILT3 can also function in antigen capture and presentation. It is efficiently internalized upon cross-linking, and delivers its ligand to an intracellular compartment where it is processed and presented to T cells. Thus, ILT3 is a novel inhibitory receptor that can negatively regulate activation of APCs and can be used by APCs for antigen uptake.

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(A) Protein tyrosine  phosphorylation stimulated by  treatment of monocytes with the  anti-HLA-DR mAb 3.8B1 is inhibited by co-ligation of HLADR with ILT3. Monocytes were  incubated with medium alone  (lane 1), with ZM3.8 mAb (antiILT3; lane 2), with 3.8B1 mAb  (anti-HLA-DR; lane 3) or with  both mAbs in the absence (lane  4) or in the presence (lane 5) of a  secondary cross-linking antibody. Cell lysates were separated on SDS-PAGE, transferred to nitrocellulose, and  probed with HRP-coupled antiphosphotyrosine mAb 4G10.  (B) Association of SHP-1 with  ILT3 is increased upon ILT3  cross-linking. Monocytes were  stimulated with ZM3.8 (lane 2)  or with a control IgG (5.133  mAb) (lane 1) coated on plastic  plates. Cells were kept at 37°C for 2 min, harvested, and lysed. ILT3 was  immunoprecipitated with ZM3.8. Proteins were separated on SDSPAGE, transferred to nitrocellulose, and probed with anti-SHP-1, followed by HRP-conjugated goat anti–rabbit Ig. The migration of SHP-1  is marked by the arrow.
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Figure 5: (A) Protein tyrosine phosphorylation stimulated by treatment of monocytes with the anti-HLA-DR mAb 3.8B1 is inhibited by co-ligation of HLADR with ILT3. Monocytes were incubated with medium alone (lane 1), with ZM3.8 mAb (antiILT3; lane 2), with 3.8B1 mAb (anti-HLA-DR; lane 3) or with both mAbs in the absence (lane 4) or in the presence (lane 5) of a secondary cross-linking antibody. Cell lysates were separated on SDS-PAGE, transferred to nitrocellulose, and probed with HRP-coupled antiphosphotyrosine mAb 4G10. (B) Association of SHP-1 with ILT3 is increased upon ILT3 cross-linking. Monocytes were stimulated with ZM3.8 (lane 2) or with a control IgG (5.133 mAb) (lane 1) coated on plastic plates. Cells were kept at 37°C for 2 min, harvested, and lysed. ILT3 was immunoprecipitated with ZM3.8. Proteins were separated on SDSPAGE, transferred to nitrocellulose, and probed with anti-SHP-1, followed by HRP-conjugated goat anti–rabbit Ig. The migration of SHP-1 is marked by the arrow.

Mentions: To test whether inhibition of Ca2+ mobilization responses was paralleled by inhibition of tyrosine phosphorylation, we performed antiphosphotyrosine immunoblotting on whole cell lysates of monocytes stimulated via HLA-DR in the absence or in the presence of co-ligation with ILT3. As shown in Fig. 5 A, monocytes triggered via HLA-DR displayed a substantial increase of tyrosine phosphorylation (lane 3), as compared to monocytes incubated with medium alone (lane 1) or with anti-ILT3 mAb (lane 2). Co-ligation of ILT3 with HLA-DR resulted in a dramatic reduction of the intensity and number of tyrosine phosphorylated species (lane 5). In the absence of secondary cross-linking antibody, ILT3 did not block HLA-DR–triggered tyrosine phosphorylation increase (lane 4).


A novel inhibitory receptor (ILT3) expressed on monocytes, macrophages, and dendritic cells involved in antigen processing.

Cella M, Döhring C, Samaridis J, Dessing M, Brockhaus M, Lanzavecchia A, Colonna M - J. Exp. Med. (1997)

(A) Protein tyrosine  phosphorylation stimulated by  treatment of monocytes with the  anti-HLA-DR mAb 3.8B1 is inhibited by co-ligation of HLADR with ILT3. Monocytes were  incubated with medium alone  (lane 1), with ZM3.8 mAb (antiILT3; lane 2), with 3.8B1 mAb  (anti-HLA-DR; lane 3) or with  both mAbs in the absence (lane  4) or in the presence (lane 5) of a  secondary cross-linking antibody. Cell lysates were separated on SDS-PAGE, transferred to nitrocellulose, and  probed with HRP-coupled antiphosphotyrosine mAb 4G10.  (B) Association of SHP-1 with  ILT3 is increased upon ILT3  cross-linking. Monocytes were  stimulated with ZM3.8 (lane 2)  or with a control IgG (5.133  mAb) (lane 1) coated on plastic  plates. Cells were kept at 37°C for 2 min, harvested, and lysed. ILT3 was  immunoprecipitated with ZM3.8. Proteins were separated on SDSPAGE, transferred to nitrocellulose, and probed with anti-SHP-1, followed by HRP-conjugated goat anti–rabbit Ig. The migration of SHP-1  is marked by the arrow.
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Related In: Results  -  Collection

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Figure 5: (A) Protein tyrosine phosphorylation stimulated by treatment of monocytes with the anti-HLA-DR mAb 3.8B1 is inhibited by co-ligation of HLADR with ILT3. Monocytes were incubated with medium alone (lane 1), with ZM3.8 mAb (antiILT3; lane 2), with 3.8B1 mAb (anti-HLA-DR; lane 3) or with both mAbs in the absence (lane 4) or in the presence (lane 5) of a secondary cross-linking antibody. Cell lysates were separated on SDS-PAGE, transferred to nitrocellulose, and probed with HRP-coupled antiphosphotyrosine mAb 4G10. (B) Association of SHP-1 with ILT3 is increased upon ILT3 cross-linking. Monocytes were stimulated with ZM3.8 (lane 2) or with a control IgG (5.133 mAb) (lane 1) coated on plastic plates. Cells were kept at 37°C for 2 min, harvested, and lysed. ILT3 was immunoprecipitated with ZM3.8. Proteins were separated on SDSPAGE, transferred to nitrocellulose, and probed with anti-SHP-1, followed by HRP-conjugated goat anti–rabbit Ig. The migration of SHP-1 is marked by the arrow.
Mentions: To test whether inhibition of Ca2+ mobilization responses was paralleled by inhibition of tyrosine phosphorylation, we performed antiphosphotyrosine immunoblotting on whole cell lysates of monocytes stimulated via HLA-DR in the absence or in the presence of co-ligation with ILT3. As shown in Fig. 5 A, monocytes triggered via HLA-DR displayed a substantial increase of tyrosine phosphorylation (lane 3), as compared to monocytes incubated with medium alone (lane 1) or with anti-ILT3 mAb (lane 2). Co-ligation of ILT3 with HLA-DR resulted in a dramatic reduction of the intensity and number of tyrosine phosphorylated species (lane 5). In the absence of secondary cross-linking antibody, ILT3 did not block HLA-DR–triggered tyrosine phosphorylation increase (lane 4).

Bottom Line: Indeed, co-ligation of ILT3 to stimulatory receptors expressed by APCs results in a dramatic blunting of the increased [Ca2+]i and tyrosine phosphorylation triggered by these receptors.It is efficiently internalized upon cross-linking, and delivers its ligand to an intracellular compartment where it is processed and presented to T cells.Thus, ILT3 is a novel inhibitory receptor that can negatively regulate activation of APCs and can be used by APCs for antigen uptake.

View Article: PubMed Central - PubMed

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

ABSTRACT
Immunoglobulin-like transcript (ILT) 3 is a novel cell surface molecule of the immunoglobulin superfamily, which is selectively expressed by myeloid antigen presenting cells (APCs) such as monocytes, macrophages, and dendritic cells. The cytoplasmic region of ILT3 contains putative immunoreceptor tyrosine-based inhibitory motifs that suggest an inhibitory function of ILT3. Indeed, co-ligation of ILT3 to stimulatory receptors expressed by APCs results in a dramatic blunting of the increased [Ca2+]i and tyrosine phosphorylation triggered by these receptors. Signal extinction involves SH2-containing protein tyrosine phosphatase 1, which is recruited by ILT3 upon cross-linking. ILT3 can also function in antigen capture and presentation. It is efficiently internalized upon cross-linking, and delivers its ligand to an intracellular compartment where it is processed and presented to T cells. Thus, ILT3 is a novel inhibitory receptor that can negatively regulate activation of APCs and can be used by APCs for antigen uptake.

Show MeSH
Related in: MedlinePlus