Key role of Free Heavy Chain of HLA class I molecules in HCMV and tumor stress sensing by gamma-delta TCR
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1
UMR 5164 CIRID, Univ. Bordeaux Segalen - CNRS, France
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2
Immunology and Immunogenetic laboratory, France
Non-Vδ2 γδ T cell clones isolated from Cytomegalovirus (HCMV)-infected individuals show dual TCR dependent reactivity against tumor cell lines and HCMV-infected cells suggesting recognition of stress-associated self antigens by non-Vδ2 TCRs. In order to identify these uncharacterized ligands, we immunize mice with tumor cells targeted by HCMV-reactive non-Vδ2 TCRs and select mAbs able to specifically abrogate the reactivity of γδ TCR transductants against these targets.
In this study, we focused on a Vγ9Vδ3 TCR, which confers to transductants a restricted reactivity against three tumor B cell lines only. By contrast, several blocking mAbs (LSM) selected to recognize Vγ9Vδ3 antigen, ubiquitously targeted HLA class I (HLA-I) molecules expressed by a wide panel of cells. These results suggested the Vγ9Vδ3 TCR recognition of HLA-I molecules expressed in a particular shape or environment in the three B cell targets. Interestingly, B cell targets and HCMV-infected cells expressed β-2-microglobulin-free HLA-I heavy chains (FHC). Silencing β-2-microglobulin in B cell targets abrogated both HLA-I FHC cell surface expression and Vγ9Vδ3 TCR reactivity, suggesting the recognition of HLA-I FHC by the Vγ9Vδ3 TCR. Moreover, the original Vγ9Vδ3 T clone expressed CD85j and CD158b inhibitory receptors specific for HLA-I, that do not bind FHC, suggesting a regulation of TCR-mediated HLA-I recognition in physiological context. Blocking these receptors markedly increased the Vγ9Vδ3 T clone reactivity against B cell targets and HCMV-infected cells.
Altogether, our results identify HLA-I FHC as a potential stress-associated antigen common to HCMV-infection or cellular transformation that mediate stress surveillance by γδ T cells.
Keywords:
gamma-delta T cells,
HLA Antigens,
ligand-receptor interaction,
CMV,
B cells
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Innate immunity
Citation:
Marlin
R,
Netzer
S,
Pitard
V,
Daburon
S,
Harly
C,
Bachelet
T,
Moreau
J,
Taupin
J and
Dechanet
J
(2013). Key role of Free Heavy Chain of HLA class I molecules in HCMV and tumor stress sensing by gamma-delta TCR
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Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00960
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Received:
25 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Julie Dechanet, UMR 5164 CIRID, Univ. Bordeaux Segalen - CNRS, Bordeaux, France, jdechanet@cirid.org