Solid tumor immunotherapy using NKG2D-based adaptor CAR T cells.

NKG2D ligands (NKG2DLs) are broadly expressed in cancer. To target these, we describe an adaptor chimeric antigen receptor (CAR) termed NKG2D/Dap10-12. Herein, T cells are engineered to co-express NKG2D with a fusion protein that comprises Dap10 joined to a Dap12 endodomain.

Mechanical control of antigen detection and discrimination by T and B cell receptors.

The adaptive immune response is orchestrated by just two cell types, T cells and B cells. Both cells possess the remarkable ability to recognize virtually any antigen through their respective antigen receptors-the T cell receptor (TCR) and B cell receptor (BCR). Despite extensive investigations into the biochemical signaling events triggered by antigen recognition in these cells, our ability to predict or control the outcome of T and B cell activation remains elusive.

Extracellular matrix rigidity modulates physical properties of subcapsular sinus macrophage-B cell immune synapses.

Subcapsular sinus macrophages (SSMs) play a key role in immune defense by forming immunological barriers that control the transport of antigens from lymph into lymph node follicles. SSMs participate in antibody responses by presenting antigens directly to naive B cells and by supplying antigens to follicular dendritic cells to propagate germinal center reactions. Despite the prominent roles that SSMs play during immune responses, little is known about their cell biology because they are technically challenging to isolate and study in vitro.

The Role and Regulation of the NKG2D/NKG2D Ligand System in Cancer.

The family of human NKG2D ligands (NKG2DL) consists of eight stress-induced molecules. Over 80% of human cancers express these ligands on the surface of tumour cells and/or associated stromal elements. In mice, NKG2D deficiency increases susceptibility to some types of cancer, implicating this system in immune surveillance for malignancy.