The Glycosylphosphatidylinositol Anchor Regulates T Cell Antigen Receptor Induced IL-2 Production

0556089 - ÚMG 2022 RIV CN eng J - Článek v odborném periodiku
Vacaresse, N. - Ferzoco, A. - Filipp, Dominik - Amemiya, Y. - Seth, A. - Andrews, D. - Kinoshita, T. - Julius, M.
The Glycosylphosphatidylinositol Anchor Regulates T Cell Antigen Receptor Induced IL-2 Production.
Open Journal of Immunology. Roč. 13, March (2021), č. článku 2076. ISSN 2162-450X. E-ISSN 2162-4526
Institucionální podpora: RVO:68378050
Klíčová slova: GPI Anchor * TCR Regulation * IL-2 Production
Obor OECD: Immunology
Způsob publikování: Omezený přístup
https://www.scirp.org/journal/oji/

Differential contributions of the glycosylphosphatidylinositol (GPI)-anchor and GPI-anchored proteins (GPI-AP) to signalling remain poorly understood. Here we show that GPI-AP deficient murine clones produce on average 18 and 181-fold more IL-2 mRNA and protein, respectively, upon T cell receptor (TCR) stimulation, in a cell-intrinsic fashion. This phenotype is formally attributed to a mutation within the transferase complex that predicates the initial step in GPI-anchor biosynthesis. Conditional disruption of the transferase complex enabled the generation of primary GPI-AP deficient CD4+ T cells, which produce on average 10- and 23-fold more IL-2 mRNA and protein, respectively, upon TCR stimulation. Conditional disruption on the transamidase complex yields GPI-sufficient, GPI-AP deficient primary CD4+ T cells. TCR stimulation of these cells yields levels of IL-2 mRNA and protein ranging from 1 - 3 and 3-fold, respectively, of controls. These results provide the first evidence of a profound impact of GPI in the regulation of TCR signalling.
Trvalý link: http://hdl.handle.net/11104/0330469