Regulation of cytotoxic T lymphocyte triggering by PIR-B on dendritic cells

Endo, Shota; Sakamoto, Yuzuru; Kobayashi, Eiji; Nakamura, Akira; Takai, Toshiyuki

doi:10.1073/pnas.0804571105

Cited by 49 publications

(38 citation statements)

References 43 publications

(47 reference statements)

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“…Microarray analysis revealed that dermal CD14 + DCs expressed ILT4 and ILT2, known inhibitors of CD8 binding to MHC class I (21,22,28). Indeed, structural modeling demonstrated that ILT2 or ILT4 sterically interfere with CD8-α in binding to MHC class I (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Interacting with MHC in the immunological synapse, a specialized junction between a T lymphocyte and an APC, CD8 can enhance the affinity of T-cell receptor (TCR)-CD8 complexes for MHC-peptide (pMHC) complexes by ∼10-fold (19). The importance of CD8 is also demonstrated by the function of two inhibitory receptors, ILT2 and ILT4, that can inhibit the function of CD8 by competing for MHC class I binding and generate T regulatory cells (20)(21)(22)(23)). …”

Section: Endritic Cells (Dcs) Are Potent Antigen-presenting Cells (mentioning

confidence: 99%

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Immunoglobulin-like transcript receptors on human dermal CD14⁺dendritic cells act as a CD8-antagonist to control cytotoxic T cell priming

Banchereau

Zurawski

Thompson-Snipes

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Human Langerhans cells (LCs) are highly efficient at priming cytolytic CD8 + T cells compared with dermal CD14 + dendritic cells (DCs). Here we show that dermal CD14 + DCs instead prime a fraction of naïve CD8 + T cells into cells sharing the properties of type 2 cytokinesecreting CD8 + T cells (TC2). Differential expression of the CD8-antagonist receptors on dermal CD14 + DCs, the Ig-like transcript (ILT) inhibitory receptors, explains the difference between the two types of DCs. Inhibition of CD8 function on LCs inhibited cytotoxic T lymphocytes (CTLs) and enhanced TC2 generation. In addition, blocking ILT2 or ILT4 on dermal CD14 + DCs enhanced the generation of CTLs and inhibited TC2 cytokine production. Lastly, addition of soluble ILT2 and ILT4 receptors inhibited CTL priming by LCs. Thus, ILT receptor expression explains the polarization of CD8 + T-cell responses by LCs vs. dermal CD14 + DCs.D endritic cells (DCs) are potent antigen-presenting cells (APCs) responsible for inducing Ag-specific immunity and tolerance (1). Several populations of DCs take up residence in different tissues and carry common as well as unique biological functions (2, 3). The healthy human skin displays at least three DC populationsLangerhans cells (LCs) in the epidermis and interstitial CD1a + and CD14 + DCs in the dermis (4, 5). Each of the different skin DC subsets carries out specialized functions. CD14 + DCs that reside in the dermis are particularly efficient at controlling the differentiation of naïve B cells into plasma cells (6, 7). Epidermal LCs, conversely, are highly efficient at priming naïve CD8 + T cells into potent cytotoxic T lymphocytes (CTLs). Both DC subsets are equally efficient at inducing a secondary CD8 + T-cell response (7-9).T lymphocytes are also composed of subsets. The CD4 + T-cell subsets, Th1 and Th2 (10), were the first to be characterized. Subsequently, other subsets have been identified and include Tregs, Th17, Tfh, and Th9 (11). CD8 + T-cell subsets have also been divided into subsets based on their cytokine production profile (12)(13)(14). Type 1 cytokine-producing T cells (TC1) express IFN-γ and TNF-α, whereas type 2 cytokine-producing T cells (TC2) produce IL-4, -5, and -13. Suppressor CD8 + T cells produce IL-10 and TGF-β and are characterized by low expression levels of CD8 and CD28 (15,16). These findings are physiologically relevant because the balance between TC1 to TC2 and CD8 + suppressor T cell populations correlates with a patient's ability to overcome tumor overgrowth or viral infections.Studies with CD8-α or CD8-β gene-targeted mice have revealed that CD8 plays a key role in the maturation and function of MHC class I-restricted T lymphocytes (17,18). Interacting with MHC in the immunological synapse, a specialized junction between a T lymphocyte and an APC, CD8 can enhance the affinity of T-cell receptor (TCR)-CD8 complexes for MHC-peptide (pMHC) complexes by ∼10-fold (19). The importance of CD8 is also demonstrated by the function of two inhibitory receptors, ILT2 and ILT4, that can...

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Section: Discussionmentioning

confidence: 99%

Section: Endritic Cells (Dcs) Are Potent Antigen-presenting Cells (mentioning

confidence: 99%

Immunoglobulin-like transcript receptors on human dermal CD14⁺dendritic cells act as a CD8-antagonist to control cytotoxic T cell priming

Banchereau

Zurawski

Thompson-Snipes

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Colonies formed were observed through a phase-contrast microscope, and their numbers were counted on the third day for CFU-E and twelfth day for BFU-E, CFU-G, CFU-M, CFU-GM, and CFU-GEMM. In certain cases, 20 kBq of 3 H-thymidine (GE Healthcare) was added to the culture of 2 × 10 4 BMMCs for 8 hours, and its incorporation into an acid-insoluble fraction was measured by a beta-counter, Matrix 9600 (Packard), according to the described method (50).…”

Section: Figurementioning

confidence: 99%

Smap1 deficiency perturbs receptor trafficking and predisposes mice to myelodysplasia

et al. 2013

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The formation of clathrin-coated vesicles is essential for intracellular membrane trafficking between subcellular compartments and is triggered by the ARF family of small GTPases. We previously identified SMAP1 as an ARF6 GTPase-activating protein that functions in clathrin-dependent endocytosis. Because abnormalities in clathrin-dependent trafficking are often associated with oncogenesis, we targeted Smap1 in mice to examine its physiological and pathological significance. Smap1-deficent mice exhibited healthy growth, but their erythroblasts showed enhanced transferrin endocytosis. In mast cells cultured in SCF, Smap1 deficiency did not affect the internalization of c-KIT but impaired the sorting of internalized c-KIT from multivesicular bodies to lysosomes, resulting in intracellular accumulation of undegraded c-KIT that was accompanied by enhanced activation of ERK and increased cell growth. Interestingly, approximately 50% of aged Smap1-deficient mice developed anemia associated with morphologically dysplastic cells of erythroid-myeloid lineage, which are hematological abnormalities similar to myelodysplastic syndrome (MDS) in humans. Furthermore, some Smap1-deficient mice developed acute myeloid leukemia (AML) of various subtypes. Collectively, to our knowledge these results provide the first evidence in a mouse model that the deregulation of clathrin-dependent membrane trafficking may be involved in the development of MDS and subsequent AML. IntroductionIntracellular and extracellular homeostasis is maintained by a vesicle transport system that mediates the trafficking of membrane proteins to appropriate organelles. Clathrin-coated vesicles are formed at donor membrane sites in a highly ordered manner, and a number of molecules are involved in this process. Among them, small GTPases of the ARF family play a central role in vesicle formation. An ARF molecule cycles between two conformations, an active GTP-bound form and an inactive GDP-bound form. This cycling is mediated by a guanine nucleotide exchange factor that replaces GDP with GTP and a GTPase-activating protein (GAP) that hydrolyzes GTP to GDP and converts ARF into its inactive form. There are 6 ARFs (ARF1-ARF6) and several ARF-related proteins in mammals (1, 2). ARF6 is an isoform that localizes mainly to the plasma membrane and functions in the endocytosis and recycling of vesicles as well as in actin rearrangement and lipid metabolism (3,4).We previously demonstrated that small ARF GAP1 (referred to as SMAP1) is a regulator of clathrin-dependent endocytosis, based on a series of observations (5, 6). First, SMAP1 exhibits GAP activity against ARF6, as assessed by an in vitro GAP assay. Second, SMAP1 localizes to juxta-plasma membrane regions in which ARF6 also exists. Third, SMAP1 binds to the clathrin heavy chain directly via its clathrin-binding box. Fourth, overexpression of SMAP1 abrogates clathrin-dependent internalization of the transferrin receptor and E-cadherin.

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“…The DNA fragments were inserted into pFUSE-hIgG1e3-Fc2 vector (InvivoGen, San Diego, CA). For the expression of PIR-A4 D1-D6 monomer, the plasmid was transfected to the DG44 cell (Invitrogen) and applied for gene amplification with methotrexate (Sigma) as described previously (20). For the expression of PIR-A4 D1D2 and D3-D6 Fc fusion protein, the plasmids were transfected to CHO-K1 cells.…”

Section: Preparation Of Recombinant Pir Domains-pir-b Likementioning

confidence: 99%

“…The fragment was inserted into pcDNA3.1 Zeo(ϩ) (Invitrogen). The resultant plasmid was further digested with BglII and NgoMIV to obtain CMV promoter-insert-poly(A) site fragment and ligated into pSV2-dhfr (ATCC) as described previously (20). PIR-A4 D1D2 and D3-D6 DNA fragments were amplified from PIR-A4 D1-D6 DNA-inserted pcDNA3.1 Zeo(ϩ) vector as a template with following primers: PIR-A4 (D1D2), 5Ј-CCATGGCCCTCCCTAAGCCTATCCTC-3Ј and 5Ј-CCATGGGGAGCTCCACGGATTCAC-3Ј; PIR-A4 (D3-D6), 5Ј-GATATCAGGTAATCTCCAAAAACCAACCAT-3Ј and 5Ј-GATATCGCTGAGACTGTGAGCTCCAC-3Ј.…”

Section: Preparation Of Recombinant Pir Domains-pir-b Likementioning

confidence: 99%

Differential but Competitive Binding of Nogo Protein and Class I Major Histocompatibility Complex (MHCI) to the PIR-B Ectodomain Provides an Inhibition of Cells

Matsushita

Endo

Kobayashi

et al. 2011

Journal of Biological Chemistry

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Binding of class I MHC molecules (MHCI) to an inhibitory receptor, PIR-B, expressed on B cells and myeloid cells provides; also known as class I H-2 and HLA in mice and humans, respectively) (6). Because MHCI are expressed ubiquitously, the binding to MHCI causes PIR-B to deliver a constitutive inhibitory signal via recruitment of tyrosine phosphatase, Src homology 2 domain-containing tyrosine phosphatase-1 (7-9), whose substrates are critical cytosolic signaling molecules such as Bruton's tyrosine kinase (10). Similar to other stimulatory and inhibitory receptor pairs with shared ligand-binding specificities (11), PIR-B expression usually takes place concomitantly with that of the activating-type isoform PIR-A although the physiological role of PIR-A in the immune system remains largely unknown.Recent unexpected findings have revealed additional inhibitory roles of PIR-B in synaptic plasticity (12) and axonal regeneration (13) in the neuronal system. In mice lacking functional PIR-B, the cortical ocular dominance plasticity is more robust, indicating that PIR-B functions to limit the extent of experience-dependent plasticity in the visual cortex and suggesting that it may function broadly to stabilize neuronal circuits (12). Surprisingly, it has also been reported (13) that PIR-B can bind to three axonal outgrowth inhibitory proteins in oligodendrocytes, i.e. neurite outgrowth inhibitor protein (Nogo) (14), myelin-associated glycoprotein (MAG) (15, 16), and oligodendrocyte myelin glycoprotein (OMgp) (17), like the Nogo receptor does (18,19). Interfering with PIR-B activity, either with antibodies or by genetic deletion of the cytoplasmic portion of PIR-B, partially reverses the neurite inhibition by Nogo, MAG, and OMgp, implying that PIR-B mediates the regeneration blocking of axons (13).Given the two kinds of physiological ligands for PIR-B, i.e. MHCI and neurite outgrowth inhibitor proteins, we were

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Regulation of cytotoxic T lymphocyte triggering by PIR-B on dendritic cells

Abstract: Priming of cytotoxic T lymphocytes (CTLs) by dendritic cells (DCs

Cited by 49 publications

References 43 publications

Immunoglobulin-like transcript receptors on human dermal CD14⁺dendritic cells act as a CD8-antagonist to control cytotoxic T cell priming

Immunoglobulin-like transcript receptors on human dermal CD14⁺dendritic cells act as a CD8-antagonist to control cytotoxic T cell priming

Smap1 deficiency perturbs receptor trafficking and predisposes mice to myelodysplasia

Differential but Competitive Binding of Nogo Protein and Class I Major Histocompatibility Complex (MHCI) to the PIR-B Ectodomain Provides an Inhibition of Cells

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Regulation of cytotoxic T lymphocyte triggering by PIR-B on dendritic cells

Abstract: Priming of cytotoxic T lymphocytes (CTLs) by dendritic cells (DCs

Cited by 49 publications

References 43 publications

Immunoglobulin-like transcript receptors on human dermal CD14+dendritic cells act as a CD8-antagonist to control cytotoxic T cell priming

Immunoglobulin-like transcript receptors on human dermal CD14+dendritic cells act as a CD8-antagonist to control cytotoxic T cell priming

Smap1 deficiency perturbs receptor trafficking and predisposes mice to myelodysplasia

Differential but Competitive Binding of Nogo Protein and Class I Major Histocompatibility Complex (MHCI) to the PIR-B Ectodomain Provides an Inhibition of Cells

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Immunoglobulin-like transcript receptors on human dermal CD14⁺dendritic cells act as a CD8-antagonist to control cytotoxic T cell priming

Immunoglobulin-like transcript receptors on human dermal CD14⁺dendritic cells act as a CD8-antagonist to control cytotoxic T cell priming