Antibodies to Interleukin-2 Elicit Selective T Cell Subset Potentiation through Distinct Conformational Mechanisms

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F15%3A00452769" target="_blank" >RIV/61388971:_____/15:00452769 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1016/j.immuni.2015.04.015" target="_blank" >http://dx.doi.org/10.1016/j.immuni.2015.04.015</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.immuni.2015.04.015" target="_blank" >10.1016/j.immuni.2015.04.015</a>

Result language

angličtina

Original language name

Antibodies to Interleukin-2 Elicit Selective T Cell Subset Potentiation through Distinct Conformational Mechanisms

Original language description

Interleukin-2 (IL-2) is a pleiotropic cytokine that regulates immune cell homeostasis and has been used to treat a range of disorders including cancer and autoimmune disease. IL-2 signals via interleukin-2 receptor-beta (IL-2R beta):IL-2R gamma heterodimers on cells expressing high (regulatory T cells, Treg) or low (effector cells) amounts of IL-2R alpha (CD25). When complexed with IL-2, certain anti-cytokine antibodies preferentially stimulate expansion of Treg (JES6-1) or effector (S4B6) cells, offering a strategy for targeted disease therapy. We found that JES6-1 sterically blocked the IL-2:IL-2R beta and IL-2:IL-2Rg interactions, but also allosterically lowered the IL-2:IL-2R alpha affinity through a "triggered exchange'' mechanism favoring IL-2R alpha hi Treg cells, creating a positive feedback loop for IL-2R alpha hi cell activation. Conversely, S4B6 sterically blocked the IL-2:IL-2R alpha interaction, while also conformationally stabilizing the IL-2:IL-2R beta interaction, thus

Czech name

—

Czech description

—

Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EC - Immunology

OECD FORD branch

—

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2015

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Immunity

ISSN

1074-7613

e-ISSN

—

Volume of the periodical

42

Issue of the periodical within the volume

5

Country of publishing house

US - UNITED STATES

Number of pages

11

Pages from-to

815-825

UT code for WoS article

000354827400009

EID of the result in the Scopus database

—