CD8‐β ADP‐ribosylation affects CD8+ T‐cell function. Issue 7 (17th May 2013)

• Record Type: Journal Article
• Authors: Lischke, Timo; Schumacher, Valéa; Wesolowski, Janusz; Hurwitz, Robert; Haag, Friedrich; Koch‐Nolte, Friedrich; Mittrücker, Hans‐Willi
• Is Part Of: European journal of immunology. Volume 43:Issue 7(2013:Jul.)
• Page Start: 1828
• Page End: 1838
• Publication Date: 2013-05-17
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201243231
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The CD8αβ coreceptor is crucial for effective peptide: MHC‐I recognition by the TCR of CD8<sup>+</sup> T cells. Adenosine diphosphate ribosyl transferase 2.2 (ART2.2) utilizes extracellular NAD<sup>+</sup> to transfer ADP‐ribose to arginine residues of extracellular domains of surface proteins. Here, we show that in the presence of extracellular NAD<sup>+</sup>, ART2.2 caused ADP‐ribosylation of CD8‐β on murine CD8<sup>+</sup> T cells in vitro and in vivo. Treatment with NAD<sup>+</sup> prevented binding of anti‐CD8‐β mAb YTS156.7.7 but not of mAb H35–17.2, indicating that NAD<sup>+</sup> caused modification of certain epitopes and not a general loss of CD8‐β. Loss of antibody binding was strictly dependent on ART2.2, because it was not observed on ART2‐deficient T cells or in the presence of inhibitory anti‐ART2.2 single‐domain antibodies. ADP‐ribosylation of CD8‐β occurred during cell isolation, particularly when cells were isolated from CD38‐deficient mice. Incubation of ART2‐expressing, but not of ART2‐deficient, OVA‐specific CD8<sup>+</sup> T cells with NAD<sup>+</sup> interfered with binding of OVA<sub>257–264</sub>:MHC‐I tetramers. In line with this result, treatment of WT mice with NAD<sup>+</sup> resulted in reduced CD8<sup>+</sup> T‐cell mediated cytotoxicity in vivo. We propose that ADP‐ribosylation of CD8‐β can regulate the coreceptor function of CD8 in the presence of elevated levels of extracellular NAD<sup>+</sup>.</p> </abstract>