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Shi and Li et al. show that SARS-CoV-2 Omicron subvariants have increased capacity to infect primary human nasal tissue using a distinct entry route that depends on matrix metalloproteinases as opposed to TMPRSS2 used by previous variants, which enables evasion from antiviral factors.

Inflammation-induced oxidative conversion of cysteine to serine in insulin creates a neoepitope that induces diabetogenic CD4⁺ T cells, revealing a mechanism for neoantigen generation that is relevant for autoimmunity, cancer and infectious disease.

CD8⁺ T cells are found within peripheral tissues including the skin. Here, the authors use an interferon-gamma reporter system and viruses expressing agonistic peptides of varying affinities to investigate how T cell receptor signaling strength changes the chemotactic properties of effector CD8⁺ T cells to promote tissue-residency.

Antigenic epitopes differ in their immunogenicity. Yewdell and colleagues show that B cell and antibody responses to influenza A virus infection display reproducible dynamic immunodominance hierarchies to viral hemagglutinin epitopes.

Making discoveries is the most important part of being a scientist, and also the most fun. This article provides practical advice to young scientists on choosing a research topic, on designing, performing and interpreting experiments and on maintaining their sanity in the process.

Although biomedical research has never been more intellectually exciting or practically important to society, pursuing a career as a biomedical scientist has never been more difficult. This article provides advice and gives tips on finding the right laboratory for Ph.D. and postdoctoral training.

An autoimmune attack on cells that make the hormone insulin causes type 1 diabetes. A mouse study reveals that pancreatic-cell release of insulin peptide fragments into the bloodstream triggers this harmful process.

Synthetic oligopeptides chemically modified with environmentally sensitive fluorophores enable real-time visualization of peptide binding to MHC molecules. This technology will expand our understanding of antigen presentation and enable visualization of fluorescent peptide binding to a wide variety of receptors in living cells.

Accurate transfer RNA (tRNA) aminoacylation is necessary for translational fidelity; however, the accuracy of tRNA aminoacylation in vivo is uncertain. In mammalian cells, approximately 1% of methionine residues used in protein synthesis are now shown to be aminoacylated to non-methionyl-tRNAs. Furthermore, misacylation of methionine increases up to tenfold upon exposing cells to viruses, toll-like receptor ligands or oxidative stress.

A recent study shows that a self-peptide generated in pancreatic islet beta cells through the translation of a noncanonical alternative reading frame in human insulin mRNA is recognized by both CD4⁺ and CD8⁺ T cells in type 1 diabetes.

Memory T cells remember viruses from previous infections, providing immunity by facilitating the killing of infected cells. For this, they exploit cross-dressing, the transfer of antigens between antigen-presenting cells. See Letter p.629

Immunosurveillance monitors subversion of the endoplasmic reticulum aminopeptidase ERAAP. ERAAP-deficient cells are killed by T cells that recognize nonclassical major histocompatibility complex class I Qa-1 molecules presenting peptides generated in the absence of ERAAP.

Structural and functional analyses of three neutralizing antibodies against influenza virus H2 HA may explain why this HA subtype has disappeared from circulation in the human population and point to a potential new avenue for antiflu therapeutics.

Lymph fluid carries cells, debris and viruses to draining lymph nodes. Hickman and colleagues show that large viruses can enter lymph node conduits and gain access to dendritic cells positioned deep within lymph nodes for efficient presentation of antigen to CD8⁺ T cells.

Thymic epithelial cells (TEC) are essential for the maturation of functional T cells, while thymus size is proportional to the overall output efficiency. Here the authors show, using transcriptome analyses, that mouse fetal TEC maintain a Myc-dependent genetic program to ensure a rapid increase in thymus size, and thereby expedited T cell generation.

Hogan et al. identify a co-immunodominant influenza peptide presented in mice by MHC-E, a nonclassical class I molecule. Notably, the peptide derives from a 16-residue alternative reading frame translated by leaky ribosome scanning of the M1 mRNA and is recognized by conventional CD8⁺ T cells.

Massively parallel reporter assays from a synthetic mRNA library identify sequence features of 5′ UTRs that control mRNA translatability and reveal ribosome-dependent and ribosome-independent mRNA-surveillance pathways.

Patients with type 2 Hermansky-Pudlak syndrome are immunodeficient. Mutations in AP-3 that prevent movement of lytic granules along microtubules in CD8⁺ T cells help explain these patients' susceptibility to infection.

Real-time microscopy is providing fresh insights in many fields of biology. Immunology is no exception, as demonstrated by striking images of the inner workings of dendritic cells.

Naive CD8⁺ T cells can be activated via dendritic cell 'cross-priming' of antigens obtained exogenously. Dendritic cells cannot cross-prime, however, after systemic activation in vivo, potentially contributing to immunosuppression associated with severe infections.

T cells are recruited into the battle against pathogens by interaction with professional antigen-presenting cells (APCs). A new study shows that this recruitment phase is short and terminates when newly activated T cells kill the activating APCs.

In this Review, the authors describe how dysregulated protein translation in cancer cells is an important source of tumour-specific peptides for immunosurveillance and how MHC class I antigen-processing and presentation pathways are manipulated by tumours for immunoevasion — information that will inform cancer immunotherapy approaches.