RESUMEN
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.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Receptores de Antígenos de Linfocitos T/genética , Animales , Humanos , RatonesRESUMEN
Most cases of congenital diaphragmatic hernia present as acute respiratory emergencies in the newborn period. Delayed presentation may be heralded by symptoms referred to the respiratory or gastrointestinal tract. An infant with unrecognized right-sided foramen of Bochdalek hernia presented with obstructive jaundice due to compression of the herniated common bile duct by the rim of the diaphragmatic defect. To our knowledge, this occurrence has not been previously observed in infancy or childhood.