scholarly journals Phenotypic knockout of the high-affinity human interleukin 2 receptor by intracellular single-chain antibodies against the alpha subunit of the receptor.

1995 ◽  
Vol 92 (8) ◽  
pp. 3137-3141 ◽  
Author(s):  
J. H. Richardson ◽  
J. G. Sodroski ◽  
T. A. Waldmann ◽  
W. A. Marasco
Keyword(s):  
Interleukin 2 ◽  
Alpha Subunit ◽  
Single Chain ◽  
Single Chain Antibodies ◽  
High Affinity ◽  
Interleukin 2 Receptor

scholarly journals Interleukin 2 receptor-targeted cytotoxicity. Interleukin 2 receptor-mediated action of a diphtheria toxin-related interleukin 2 fusion protein.

1988 ◽  
Vol 167 (2) ◽  
pp. 612-622 ◽  
Author(s):  
P Bacha ◽  
D P Williams ◽  
C Waters ◽  
J M Williams ◽  
J R Murphy ◽  
...  
Keyword(s):  
T Cells ◽  
Protein Synthesis ◽  
T Cell ◽  
Diphtheria Toxin ◽  
Interleukin 2 ◽  
Elongation Factor ◽  
High Affinity ◽  
Interleukin 2 Receptor ◽  
Human T Cell ◽  
Inhibition Of Protein Synthesis

The IL-2 toxin-mediated inhibition of protein synthesis in high affinity IL-2-R-positive murine and human T cell lines has been examined. Both excess free IL-2 and mAb to the Tac epitope of the p55 subunit of IL-2-R are shown to block the action of IL-2 toxin; whereas, agents that interact with other receptors or antigens on the T cell surface have no effect. We show that IL-2 toxin, like diphtheria toxin, must pass through an acidic vesicle in order to intoxicate target T cells. Finally, we demonstrate that the IL-2 toxin-mediated inhibition of protein synthesis in both human and murine T cells that bear the high affinity IL-2-R is due to the classic diphtheria toxin fragment A-catalyzed ADP ribosylation of elongation factor 2.

scholarly journals Solution assembly of the pseudo-high affinity and intermediate affinity interleukin-2 receptor complexes

2008 ◽  
Vol 8 (3) ◽  
pp. 482-489 ◽  
Author(s):  
Zining Wu ◽  
Byron Goldstein ◽  
Thomas M. Laue ◽  
Stefano F. Liparoto ◽  
Michael J. Nemeth ◽  
...  
Keyword(s):  
Interleukin 2 ◽  
Receptor Complexes ◽  
High Affinity ◽  
Interleukin 2 Receptor

Stepwise formation of the high-affinity complex of the interleukin 2 receptor

1990 ◽  
Vol 2 (12) ◽  
pp. 1167-1177 ◽  
Author(s):  
Yuji Saito ◽  
Toshihiko Ogura ◽  
Masanori Kamio ◽  
Hisataka Sabe ◽  
Takashi Uchiyama ◽  
...  
Keyword(s):  
Interleukin 2 ◽  
High Affinity ◽  
Interleukin 2 Receptor ◽  
Stepwise Formation

Novel interleukin-2 receptor subunit detected by cross-linking under high-affinity conditions

Science ◽  
1986 ◽  
Vol 234 (4778) ◽  
pp. 859-863 ◽  
Author(s):  
M Sharon ◽  
R. Klausner ◽  
B. Cullen ◽  
R Chizzonite ◽  
W. Leonard
Keyword(s):  
Interleukin 2 ◽  
Cross Linking ◽  
Receptor Subunit ◽  
High Affinity ◽  
Interleukin 2 Receptor

scholarly journals A Chimera of Interleukin 2 and a Binding Variant of Aerolysin Is Selectively Toxic to Cells Displaying the Interleukin 2 Receptor

2007 ◽  
Vol 283 (3) ◽  
pp. 1572-1579 ◽  
Author(s):  
Milan Osusky ◽  
Lisa Teschke ◽  
Xiaoying Wang ◽  
Kevin Wong ◽  
J. Thomas Buckley
Keyword(s):  
Cell Death ◽  
Mammalian Cells ◽  
Therapeutic Agent ◽  
Interleukin 2 ◽  
Bacterial Toxin ◽  
Hybrid Protein ◽  
High Affinity ◽  
Interleukin 2 Receptor ◽  
Hybrid Molecules ◽  
N Terminus

Aerolysin is a bacterial toxin that binds to glycosylphosphatidylinositol-anchored proteins (GPI-AP) on mammalian cells and oligomerizes, inserting into the target membranes and forming channels that cause cell death. We have made a variant of aerolysin, R336A, that has greatly reduced the ability to bind to GPI-AP, and as a result it is only very weakly active. Fusion of interleukin 2 (IL2) to the N terminus of R336A-aerolysin results in a hybrid that has little or no activity against cells that do not have an IL2 receptor because it cannot bind to the GPI-AP on the cells. Strikingly, the presence of the IL2 moiety allows this hybrid to bind to cells displaying high affinity IL2 receptors. Once bound, the hybrid molecules form insertion-competent oligomers. Cell death occurs at picomolar concentrations of the hybrid, whereas the same cells are insensitive to much higher concentrations of R336A-aerolysin lacking the IL2 domain. The targeted channel-forming hybrid protein may have important advantages as a therapeutic agent.

scholarly journals Recombinant immunotoxins containing anti-Tac(Fv) and derivatives of Pseudomonas exotoxin produce complete regression in mice of an interleukin-2 receptor-expressing human carcinoma

Blood ◽  
1994 ◽  
Vol 83 (2) ◽  
pp. 426-434 ◽  
Author(s):  
RJ Kreitman ◽  
P Bailon ◽  
VK Chaudhary ◽  
DJ FitzGerald ◽  
I Pastan
Keyword(s):  
Interleukin 2 ◽  
Target Cells ◽  
Complete Regression ◽  
Single Chain ◽  
Pseudomonas Exotoxin ◽  
Gene Encoding ◽  
Human Carcinoma ◽  
Interleukin 2 Receptor ◽  
Variable Domains

Anti-Tac(Fv)-PE40 is a recombinant single-chain immunotoxin composed of the variable domains of the monoclonal antibody anti-Tac, which binds to the p55 subunit of the interleukin-2 receptor (IL-2R), and a truncated form of Pseudomonas exotoxin (PE), which does not bind to the PE receptor (Chaudhary et al, Nature 339:394, 1989). Whereas its cytotoxic activity toward autoimmune and malignant target cells has been established, its efficacy in vivo remains unknown. To establish an animal model, we produced ATAC-4 cells by transfecting the gene encoding the low-affinity IL-2R (p55) into A431 epidermoid carcinoma cells. ATAC-4 cells contained low-affinity IL-2Rs (2 x 10(5)/cell) and formed tumors in nude mice. In tissue culture, protein synthesis in ATAC-4 cells was inhibited 50% (IC50) at 0.06 ng/mL (0.9 pmol/L) of anti-Tac(Fv)-PE40. IC50s for the derivatives anti-Tac(Fv)-PE38, which is missing PE amino acids 365–380, and anti-Tac(Fv)-PE38KDEL, which contains the same deletion plus the KDEL carboxyl terminus, were 0.04 and 0.025 ng/mL, respectively. All the agents produced complete tumor regressions in ATAC-4 tumor-bearing mice and anti-Tac(Fv)-PE38KDEL had significant antitumor activity at 1% of the LD50. The dose limiting toxicity of anti-Tac(Fv)-PE38KDEL was from hemorrhagic liver necrosis, which was observed at approximately 55% of the LD50.

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