CD8-β ADP-ribosylation affects CD8(+) T-cell function
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CD8-β ADP-ribosylation affects CD8(+) T-cell function. / Lischke, Timo; Schumacher, Valéa; Wesolowski, Janusz; Hurwitz, Robert; Haag, Friedrich; Nolte, Friedrich; Mittrücker, Hans-Willi.
In: EUR J IMMUNOL, Vol. 43, No. 7, 01.07.2013, p. 1828-38.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - CD8-β ADP-ribosylation affects CD8(+) T-cell function
AU - Lischke, Timo
AU - Schumacher, Valéa
AU - Wesolowski, Janusz
AU - Hurwitz, Robert
AU - Haag, Friedrich
AU - Nolte, Friedrich
AU - Mittrücker, Hans-Willi
N1 - © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2013/7/1
Y1 - 2013/7/1
N2 - The CD8αβ coreceptor is crucial for effective peptide: MHC-I recognition by the TCR of CD8(+) T cells. Adenosine diphosphate ribosyl transferase 2.2 (ART2.2) utilizes extracellular NAD(+) to transfer ADP-ribose to arginine residues of extracellular domains of surface proteins. Here, we show that in the presence of extracellular NAD(+) , ART2.2 caused ADP-ribosylation of CD8-β on murine CD8(+) T cells in vitro and in vivo. Treatment with NAD(+) prevented binding of anti-CD8-β mAb YTS156.7.7 but not of mAb H35-17.2, indicating that NAD(+) 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(+) T cells with NAD(+) interfered with binding of OVA257-264 :MHC-I tetramers. In line with this result, treatment of WT mice with NAD(+) resulted in reduced CD8(+) 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(+) .
AB - The CD8αβ coreceptor is crucial for effective peptide: MHC-I recognition by the TCR of CD8(+) T cells. Adenosine diphosphate ribosyl transferase 2.2 (ART2.2) utilizes extracellular NAD(+) to transfer ADP-ribose to arginine residues of extracellular domains of surface proteins. Here, we show that in the presence of extracellular NAD(+) , ART2.2 caused ADP-ribosylation of CD8-β on murine CD8(+) T cells in vitro and in vivo. Treatment with NAD(+) prevented binding of anti-CD8-β mAb YTS156.7.7 but not of mAb H35-17.2, indicating that NAD(+) 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(+) T cells with NAD(+) interfered with binding of OVA257-264 :MHC-I tetramers. In line with this result, treatment of WT mice with NAD(+) resulted in reduced CD8(+) 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(+) .
KW - Adenosine Diphosphate Ribose
KW - Animals
KW - Antigens, CD8
KW - CD8-Positive T-Lymphocytes
KW - Cell Separation
KW - Flow Cytometry
KW - Lymphocyte Activation
KW - Mice
KW - Mice, Inbred C57BL
KW - NAD
U2 - 10.1002/eji.201243231
DO - 10.1002/eji.201243231
M3 - SCORING: Journal article
C2 - 23575529
VL - 43
SP - 1828
EP - 1838
JO - EUR J IMMUNOL
JF - EUR J IMMUNOL
SN - 0014-2980
IS - 7
ER -