Identification of a tumor-specific allo-HLA-restricted γδTCR.
Document Type
Article
Publication Date
10-8-2019
Keywords
JMG
JAX Source
Blood Adv 2019 Oct 8; 3(19):2870-2882
Volume
3
Issue
19
First Page
2870
Last Page
2882
ISSN
2473-9537
PMID
31585951
DOI
https://doi.org/10.1182/bloodadvances.2019032409
Grant
CA034196
Abstract
γδT cells are key players in cancer immune surveillance because of their ability to recognize malignant transformed cells, which makes them promising therapeutic tools in the treatment of cancer. However, the biological mechanisms of how γδT-cell receptors (TCRs) interact with their ligands are poorly understood. Within this context, we describe the novel allo-HLA-restricted and CD8α-dependent Vγ5Vδ1TCR. In contrast to the previous assumption of the general allo-HLA reactivity of a minor fraction of γδTCRs, we show that classic anti-HLA-directed, γδTCR-mediated reactivity can selectively act on hematological and solid tumor cells, while not harming healthy tissues in vitro and in vivo. We identified the molecular interface with proximity to the peptide-binding groove of HLA-A*24:02 as the essential determinant for recognition and describe the critical role of CD8 as a coreceptor. We conclude that alloreactive γδT-cell repertoires provide therapeutic opportunities, either within the context of haplotransplantation or as individual γδTCRs for genetic engineering of tumor-reactive T cells.
Recommended Citation
Kierkels G,
Scheper W,
Meringa A,
Johanna I,
Beringer D,
Janssen A,
Schiffler M,
Aarts-Riemens T,
Kramer L,
Straetemans T,
Heijhuurs S,
Leusen J,
San José E,
Fuchs K,
Griffioen M,
Falkenburg J,
Bongiovanni L,
de Bruin A,
Vargas-Diaz D,
Altelaar M,
Heck A,
Shultz LD,
Ishikawa F,
Nishimura M,
Sebestyén Z,
Kuball J.
Identification of a tumor-specific allo-HLA-restricted γδTCR. Blood Adv 2019 Oct 8; 3(19):2870-2882