T-cell receptor articles from across Nature Portfolio

Prediction of the specificity of a T cell receptor from amino acid sequence has been performed using different methods and approaches. Here the authors use TCRab sequences with known specificity to develop a deep learning TCR-epitope interaction predictor and use this method to predict specificity of dual alpha chain TCRs and TCRs specific for different antigens.

The use of TCR engineered T cells holds promise for treatment of tumours, but is limited by awareness of clinically effective TCR molecules. Here the authors identify an MHC II restricted TCR that targets viral E7 of human papillomavirus type 18 and show effectivity in a murine model of solid tumour.

Regulation of thymocyte development by RNA-binding proteins is not fully characterized. Here the authors show the RBP ARPP21 interacting with the Rag1 3’-UTR to promote Rag1 expression, TCR rearrangement and an increased diversity of the TCR repertoire and that ARPP21 is down regulated by TCR stimulation.

The T cell receptor β-chain is expressed in two isoforms, TRBC1 and TRBC2, with clonally expanded mature T cell lymphomas expressing one of them exclusively, while healthy T cells randomly express either TRBC1 or TRBC2. Here authors show structure-based design of a TRBC2-specific antibody, and depletion of malignant T cells carrying TRBC1 or TRBC2 with CAR-T cells against the cognate receptor chain in murine models.

Autoreactive T cells that target myelin antigens in the peripheral nerves are present in patients with the demyelinating form of Guillain–Barré syndrome, and these T cells are likely to contribute to disease pathophysiology.

This Review provides an updated assessment of the expanding family of T cell-activating bacterial superantigens, emphasizing potential roles of these toxins in various disease states as well as their contribution to the evolution of the bacterial pathogens Staphylococcus aureus and Streptococcus pyogenes.

A study in Science reports 10 individuals with pre-TCRα deficiency who have late-onset or no clinical phenotype, which suggests that αβ T cells can develop through a pre-TCRα-independent, non-canonical rescue pathway.

Human mucosal-associated invariant T (MAIT) cells exhibit many functions, but whether this reflects different subsets is unknown. We defined the transcriptional and clonal landscape of MAIT cells in human blood and liver. Our study reveals limited transcriptional variation within tissues, but marked phenotypic and functional plasticity according to tissue, clone, and most notably, stimulus.

Gillian Griffiths and colleagues show that T cell receptor downregulation at the immune synapse occurs through ectocytosis, which terminates receptor signalling and promotes dissociation from target cells.

On 15–16 June 2022, the National Institute of Allergy and Infectious Diseases hosted a virtual workshop on the topic of T cell technologies to discuss assays, novel technology development, bench and clinical application of those technologies, and challenges and innovations in the field.