MS4A4B is a GITR-associated membrane adapter, expressed by regulatory T cells, which modulates T cell activation
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Description
In the aftermath of thymic negative selection, natural and adaptive regulatory T cells (Tregs) must acknowledge peripheral, “danger-free” self-Ag to ensure their sustained activity. In this paper, we show that natural and adaptive Tregs or T cells transduced with cDNA for Foxp3, just like Th1 cells, express members of the MS4A family of transmembrane molecules. Naive T cells transduced with MS4A4B become able to respond to lower levels of Ag. Using two family members, MS4A4B and MS4A6B, as baits in a yeast split-ubiquitin Treg library screen, we demonstrate their interaction with each other and with GITR, Orai1, and other surface receptors. Interaction of 4B with GITR augments GITR signaling and T cell IL-2 production in response to triggering with GITR ligand or anti-GITR Abs. This interaction provides a mechanism whereby MS4A family members, through lateral coassociation with costimulatory molecules, may amplify Ag signals. We propose that T cells preoccupied with immune defense use this MS4A family to enhance sensitivity to extrinsic Ag stimulation, ensuring its elimination, while Tregs use these adaptors to allow low level Ag signals to sustain regulatory function.
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ID Code: | 202379 | ||
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Item Type: | Contribution to Journal (Journal Article) | ||
Refereed: | Yes | ||
ORCID iD: |
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Measurements or Duration: | 8 pages | ||
DOI: | 10.4049/jimmunol.0901070 | ||
ISSN: | 0022-1767 | ||
Pure ID: | 63566165 | ||
Divisions: | Past > QUT Faculties & Divisions > Faculty of Health | ||
Copyright Owner: | Consult author(s) regarding copyright matters | ||
Copyright Statement: | This work is covered by copyright. Unless the document is being made available under a Creative Commons Licence, you must assume that re-use is limited to personal use and that permission from the copyright owner must be obtained for all other uses. If the document is available under a Creative Commons License (or other specified license) then refer to the Licence for details of permitted re-use. It is a condition of access that users recognise and abide by the legal requirements associated with these rights. If you believe that this work infringes copyright please provide details by email to qut.copyright@qut.edu.au | ||
Deposited On: | 22 Jul 2020 04:30 | ||
Last Modified: | 03 Mar 2024 19:21 |
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