Sensing cellular stress by human Gamma-Delta TCR
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1
UMR 5164 CIRID, France
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2
CRCNA, INSERM UMR892, CNRS UMR6299, France
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3
Immunology and Immunogenetic laboratory, France
Human non-Vδ2γδ T cells constitute a first line of defence in epithelium and organs by recognizing modified cells as virus infected or transformed cells. This reactivity suggests recognition of stress-associated self-antigens by non-Vδ2 TCRs. In order to identify these uncharacterized antigens, we set up a strategy comprising mice immunization with tumor cells targeted by non-Vδ2 TCRs and selection of mAbs able to specifically abrogate the reactivity of γδ TCR transductants against these targets.
In this study, we focused on a Vγ8Vδ3 TCR, which conferred to transductant a restricted reactivity against U373MG glioblastoma cell line. A blocking mAb (FMS-01) was generated against U373MG that specifically abrogated recognition by both Vγ8Vδ3 transductant and T cell clone, suggesting that FMS-01 mAb targets the antigenic ligand of Vγ8Vδ3 TCR. Surprisingly, we showed that modification of U373MG culture conditions as high level cell confluence, thermic choc, hypoxic stress or CMV infection, increased the reactivity of Vγ8Vδ3 transductant and T cell clone. These stress conditions were able to induce Vγ8Vδ3 transductant activation against other glioblastoma cell lines (U343MG and U251MG). This recognition of stressed cells was TCR dependent and blocked by FMS-01 mAb. Moreover, stress increased expression of FMS-01 targeted antigen that directly correlated with Vγ8Vδ3 transductant activation. Identification of FMS-01 targeted antigen is in process.
In conclusion, our results show that stress conditions can induce the expression of γδ TCR antigens. Because these antigens are critical for γδ T cell recognition, their identification could lead to new immunotherapeutical treatments in cancer such as glioma.
Keywords:
gamma-delta T cells,
Antigens,
surveillance,
Stress mechanics,
Glioblastoma
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Innate immunity
Citation:
Marlin
R,
Kaminski
H,
Netzer
S,
Pitard
V,
Harly
C,
Scotet
E,
Moreau
J and
Déchanet-Merville
J
(2013). Sensing cellular stress by human Gamma-Delta TCR.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.01154
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Received:
15 Jul 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Julie Déchanet-Merville, UMR 5164 CIRID, Bordeaux, France, jdechanet@immuconcept.org