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Godfrey, Pellicci and colleagues define the developmental stages and checkpoints for the development of mucosal-associated invariant T cells in humans and mice.

Attachment of a piece of viral protein to a small RNA achieves transfer of the RNA into neuronal cells in cell culture. This was also able to deliver an antiviral siRNA specifically into the brains of mice infected with encephalitis and achieve 80% protection. This study opens a new potential line of treatment for neuronal disease.

Streptococcus pyogenes causes ~750 million infections and more than 500,000 deaths each year. In this study, human volunteers were challenged with S. pyogenes and participants that developed pharyngitis had elevated levels of cytokines, and increased migration and activation of immune cells.

Natural killer T cells (NKT cells) recognize lipid antigens presented by CD1d. Zajonc and Rossjohn and their colleagues describe molecular interactions between type II NKT cell antigen receptors and CD1d-ligand complexes, which demonstrate distinct modes of recognition used by the receptors.

In contrast to microbial natural killer T cell ligands, self glycolipid antigens are β-linked. Rossjohn and co-workers provide the mechanism for the autoreactivity of natural killer T cell antigen receptors toward β-glycosylated agonists.

The invariant αβTCR of type I NKT cells recognizes a lipid α-GalCer presented by CD1d. Here the authors describe atypical α-GalCer-reactive NKT cells with diverse TCRs, which bind to CD1d-α-GalCer in a manner distinct from type I NKT cells, thus unveiling greater diversity in lipid antigen recognition.

Natural killer T cells (NKT cells) recognize lipid-based antigens presented by CD1d. The mammalian glycolipid β-glucosylceramide, a ubiquitous self antigen for NKT cells, is upregulated by microbial danger signals, which leads to activation of NKT cells in the absence of foreign glycolipid antigen.

CD1a presents a broad repertoire of lipid-based antigens. Rossjohn and colleagues show that the TCR docks over CD1a in a manner that precludes contact with permissive antigens, while nonpermissive antigens disrupt the TCR-CD1a contact.

Natural killer T (NKT) cells include type I that express semi-invariant T cell receptor (TCR), and type II that cover a broader repertoire. Here the authors describe the crystal structure of a type II NKT TCR complexed with CD1d/antigen to propose that type II NKT TCRs may adapt multiple CD1d docking modes to maximise antigen recognition efficacy.

Aspergillus fumigatus is a fungus that is associated with a severe form of asthma, although the precise immunological basis for this disease is unclear. A new study in mice shows that natural killer T (NKT) cells are crucial for progression of A. fumigatus–induced asthma and also identifies a glycolipid antigen from this fungus that seems to drive this NKT cell–mediated inflammatory response (pages 1297–1304).

Rossjohn, van der Vliet and colleagues develop single-domain antibodies binding composite CD1d and NKT T-cell receptor antigens, inducing specific antitumor immune subsets.

Children with SARS-CoV-2 infection are more likely to have mild symptoms and may be asymptomatic, but underlying reasons remain unclear. Here, the authors show cellular, cytokine and antibody response to SARS-CoV-2 infection in three children who repeatedly tested negative for the virus by PCR, despite high exposure in the household.

Mucosal-associated invariant T (MAIT) cells express invariant TRAV1/TRAJ33 TCR-α gene segments and detect antigens presented by MR1. Here the authors show that atypical, MR1-restricted MAIT populations that include both Trav1⁺ and Trav1- cells are found in both Traj33-deficient mice and human peripheral blood.

Tissue-resident memory T (T_RM) cells are distributed throughout the body as relatively sessile populations. Mackay and colleagues find that the tissue in which T_RM cells are generated dictates their properties and is in turn defined according to T_RM-cell-intrinsic sensitivity to signaling via the cytokine TGFβ.

Type I natural killer T cells are characterized by an invariant V_α14-J_α18 T cell antigen receptor α-chain. Godfrey and colleagues describe a population of CD1d-restricted natural killer T cells that express a previously unidentified canonical V_α10-J_α50 α-chain.

Wurzel et al. describe the kinetics of the immune response in relation to clinical and virological features in a 5-month old infant with congenital heart disease and severe COVID-19. The immune response was characterised by an elevated inflammatory response in the acute phase of infection, followed by Th2 skewing and prolonged T cell activation.

How γδ TCRs bind antigen presented by antigen-presenting molecules remains unclear. Godfrey and colleagues describe a population of human γδ T cells that interacts with CD1d and provide a molecular basis for how a γδ TCR binds CD1d–α-GalCer.

Antibody responses to SARS-CoV-2 are critical in the immune response to infection, but the potential cross-reactivity to other human corona viruses is poorly appreciated. Here the authors apply a systems based approach to characterise the antibody response in pre-pandemic cohorts and assess heterotypic reactivity to SARS-CoV-2.

Here, the authors discuss how the T cell receptors expressed by natural killer T cells are able to recognize and respond to an array of self and foreign lipid antigens that are presented on CD1d molecules. They explain how a better understanding of these processes could be exploited for therapeutic purposes.

The authors compare the thymic development of several innate-like T cell populations, including natural killer T cells, mucosal-associated invariant T cells and γδ T cells. They focus on the cytokines, surface molecules and transcription factors that are necessary for the development of these cells and highlight some of the key differences from conventional T cell development.