Analysis of the biological functions and fine specificity of (T,G)-A--L specific. T cell clones

Axelrod, Ofra; Mozes, Edna

doi:10.1016/s0171-2985(86)80056-0

Cited by 31 publications

(12 citation statements)

References 28 publications

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“…After 4 days of incubation, cells were washed and resuspended in 5 ml of enriched RPMI medium 1640 supplemented with 10% FCS and 2 ng͞ml of recombinant murine IL-2 (PeproTech, Rocky Hill, NJ). Cells were exposed to the stimulating peptide (5 g͞ml) presented on irradiated (3,000 rad) syngeneic spleen cells every 14 days (27) and were maintained between stimulations in enriched medium containing IL-2. For all of the experiments, cells of the line were harvested 7 days after antigenic stimulation.…”

Section: Methodsmentioning

confidence: 99%

Suppression of myasthenogenic responses of a T cell line by a dual altered peptide ligand by induction of CD4⁺CD25⁺regulatory cells

Aruna

Sela

Mozes

2005

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

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Myasthenia gravis is a T cell-dependent, antibody-mediated autoimmune disease. A dual altered peptide ligand (APL) that is composed of the tandemly arranged two single amino acid analogs of two myasthenogenic peptides, p195–212 and p259–271, was demonstrated to down-regulate in vitro and in vivo myasthenia gravis-associated autoreactive responses. The aims of this study were to demonstrate the suppressive properties and to elucidate the mechanism of action of the dual APL on a T cell line specific to the myasthenogenic peptide p195–212. We demonstrate here that incubation of cells of the line with the dual APL resulted in the inhibition of proliferation and secretion of IL-2 and IFN-γ triggered by p195–212. In contrast, secretion of TGF-β and IL-10 was upregulated. The dual APL induced the generation of CD4+CD25+ cells that were characterized by the expression of CD45Rblow, cytotoxic T lymphocyte-associated antigen-4, TGF-β, CD62L, Foxp3, and neuropilin. In addition, the dual APL-treated cells were capable of inhibiting the proliferation response of the line when the two sets of cells were cocultured. The role of CD4+CD25+ cells was further confirmed by demonstrating that the suppression was abrogated by blocking/neutralization of CD25. Thus, the dual APL acts by inducing the formation of CD4+CD25+ regulatory cells. By using a T cell line, we could show that the immunosuppressive CD4+CD25+ cells were indeed induced by the dual APL and are not part of the naturally occurring regulatory cells

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Section: Methodsmentioning

confidence: 99%

Suppression of myasthenogenic responses of a T cell line by a dual altered peptide ligand by induction of CD4⁺CD25⁺regulatory cells

Aruna

Sela

Mozes

2005

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

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“…Antibody levels specific to the different peptides in the sera of patients and healthy control individuals were determined by solid phase RIA (8). Plates were coated with 100 ul of 50 Ag/ml AChR peptides in PBS containing 0.2% glutaraldehyde and washed with PBS HLA examination.…”

Section: Methodsmentioning

confidence: 99%

In vitro proliferative responses and antibody titers specific to human acetylcholine receptor synthetic peptides in patients with myasthenia gravis and relation to HLA class II genes.

Brocke¹,

Brautbar²,

Steinman³

et al. 1988

J. Clin. Invest.

120

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To investigate which parts of the acetylcholine receptor are involved in the initiation and development of myasthenia gravis (MG), peptides representing different sequences of the human acetylcholine receptor a-subunit were synthesized. These peptides were tested for their ability to stimulate T cells of myasthenic patients and healthy control patients in proliferation assays and to bind to sera antibodies. Three of eight peptides discriminated significantly between the two groups in the proliferation assay, as well as in their ability to bind to serum antibodies. HLA-DR3 and DR5 were associated with proliferative responses to specific AChR peptides in the group of myasthenics. Acetylcholine receptor epitopes that might play a specific role in myasthenia gravis thus were demonstrated.

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“…After 4 days of incubation, cells were washed and resuspended in 5 ml of enriched RPMI medium 1640 supplemented with 10% FCS and 2 ng/ml recombinant murine IL-2 (Peprotech). Cells were exposed to the stimulating peptide (5 g/ml) presented on irradiated (3,000 rad) syngeneic spleen cells every 14 days (34) and were maintained between stimulations in enriched medium containing IL-2. For all experiments, cells of the line were used 7 days after antigenic stimulation.…”

mentioning

confidence: 99%

A 50-kDa ERK-like protein is up-regulated by a dual altered peptide ligand that suppresses myasthenia gravis-associated responses

Ben-David¹,

Aruna²,

Seger

et al. 2006

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

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Myasthenia gravis (MG) and its animal model, experimental autoimmune MG (EAMG), are T cell-dependent antibody-mediated autoimmune diseases. A dual altered peptide ligand (APL) that is composed of the tandemly arranged two single amino acid analogues of two myasthenogenic peptides, p195-212 and p259 -271, down-regulated in vitro and in vivo MG-associated autoreactive responses. The dual APL was shown to exert its beneficial effects by up-regulating ERK1,2 in CD4 ؉ CD25 ؉ regulatory cells. In this study, we investigated a novel 50-kDa ERK-like protein (ERK-50) that is up-regulated significantly in addition to ERK1,2 after treatment with the dual APL. We report here that ERK-50 was upregulated in LN cells and in LN-derived T cells of mice that were immunized with the myasthenogenic peptides and treated with the dual APL. Moreover, ERK-50 was up-regulated in dual-APLtreated mice that were immunized with the Torpedo acetylcholine receptor. ERK-50 was demonstrated to be recognized by antibodies directed against the C and N termini of ERK1, against the C terminus of ERK2, and against general ERK. The 50-kDa ERK was shown to be stimulated by Con A, and inhibition of MEK1 down-regulated the 50-kDa ERK as was shown for ERK1,2. However, 4␤-phorbol 12-myristate 13-acetate (TPA) did not stimulate ERK-50. Finally, the activated ERK-50 was up-regulated in the dual-APL-induced CD4 ؉ CD25 ؉ regulatory cells. Thus, ERK-50 is suggested to be a novel ERK isoform, being up-regulated in response to treatment with the dual APL.autoimmunity ͉ immunomodulation ͉ kinase

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Analysis of the biological functions and fine specificity of (T,G)-A--L specific. T cell clones

Cited by 31 publications

References 28 publications

Suppression of myasthenogenic responses of a T cell line by a dual altered peptide ligand by induction of CD4⁺CD25⁺regulatory cells

Suppression of myasthenogenic responses of a T cell line by a dual altered peptide ligand by induction of CD4⁺CD25⁺regulatory cells

In vitro proliferative responses and antibody titers specific to human acetylcholine receptor synthetic peptides in patients with myasthenia gravis and relation to HLA class II genes.

A 50-kDa ERK-like protein is up-regulated by a dual altered peptide ligand that suppresses myasthenia gravis-associated responses

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Analysis of the biological functions and fine specificity of (T,G)-A--L specific. T cell clones

Cited by 31 publications

References 28 publications

Suppression of myasthenogenic responses of a T cell line by a dual altered peptide ligand by induction of CD4+CD25+regulatory cells

Suppression of myasthenogenic responses of a T cell line by a dual altered peptide ligand by induction of CD4+CD25+regulatory cells

In vitro proliferative responses and antibody titers specific to human acetylcholine receptor synthetic peptides in patients with myasthenia gravis and relation to HLA class II genes.

A 50-kDa ERK-like protein is up-regulated by a dual altered peptide ligand that suppresses myasthenia gravis-associated responses

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Suppression of myasthenogenic responses of a T cell line by a dual altered peptide ligand by induction of CD4⁺CD25⁺regulatory cells

Suppression of myasthenogenic responses of a T cell line by a dual altered peptide ligand by induction of CD4⁺CD25⁺regulatory cells