Featured
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Structures of human γδ T cell receptor–CD3 complex
- Weizhi Xin
- , Bangdong Huang
- & Qiang Zhou
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Article
| Open Access
Distal colonocytes targeted by C. rodentium recruit T-cell help for barrier defence
The murine enteropathogen Citrobacter rodentium targets a specific subset of absorptive intestinal epithelial cells in the mid–distal colon, which stimulate T cells to produce sustained IL-22 signals to mitigate further spread of the pathogen.
- Carlene L. Zindl
- , C. Garrett Wilson
- & Casey T. Weaver
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Article
| Open Access
Immune microniches shape intestinal Treg function
Studies in mice show that effector T regulatory cells in the gut are most functional in the lamina propria, but this homeostatic niche is disrupted in inflammation, suggesting a spatial mechanism of tolerance to commensal microorganisms.
- Yisu Gu
- , Raquel Bartolomé-Casado
- & Fiona Powrie
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Venous-plexus-associated lymphoid hubs support meningeal humoral immunity
Dural-associated lymphoid tissues are lymphoid structures around vascular hubs in the dura mater that sample antigens and rapidly support humoral immune responses after local pathogen challenge.
- Zachary Fitzpatrick
- , Nagela Ghabdan Zanluqui
- & Dorian B. McGavern
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Bone marrow plasma cells require P2RX4 to sense extracellular ATP
We demonstrate the role of the ligand-gated purinergic ion channel P2RX4 in maintaining mouse plasma cells in their bone marrow niche.
- Masaki Ishikawa
- , Zainul S. Hasanali
- & Avinash Bhandoola
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Article
| Open Access
Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting
Exposure to early variants of SARS-CoV-2 results in immune imprinting in mouse models and in humans, reducing neutralizing antibody titres against Omicron variants, which could be mitigated with multiple updated boosters.
- Ayijiang Yisimayi
- , Weiliang Song
- & Yunlong Cao
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Article
| Open Access
Distinguishing features of long COVID identified through immune profiling
Individuals with long COVID show marked biological changes in cortisol and immune factors relative to convalescent populations.
- Jon Klein
- , Jamie Wood
- & Akiko Iwasaki
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Article
| Open Access
Neutralization, effector function and immune imprinting of Omicron variants
Convergent mutations in hot spots of the spike proteins of currently circulating SARS-CoV-2 Omicron variants increase the binding affinity for the host receptor and promote more efficient fusion with host cell membranes.
- Amin Addetia
- , Luca Piccoli
- & David Veesler
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Metabolic programs of T cell tissue residency empower tumour immunity
A study describes the metabolic adaptations supporting differentiation, survival and function of tissue-resident memory CD8+ T cells and how to leverage them to enhance immunity against pathogens and tumours.
- Miguel Reina-Campos
- , Maximilian Heeg
- & Ananda W. Goldrath
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Article
| Open Access
SLC38A2 and glutamine signalling in cDC1s dictate anti-tumour immunity
Competition for glutamine between type-1 conventional dendritic cells and tumour cells has a central role in tuning the anti-tumour immune response and in immune evasion by cancer cells.
- Chuansheng Guo
- , Zhiyuan You
- & Hongbo Chi
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Article
| Open Access
Origin and evolutionary malleability of T cell receptor α diversity
TCRα repertoire diversity is best explained by species-specific extents of sequence microhomologies marking the ends of recombining elements, and germline sequence composition of rearranging elements determines the degree of diversity of somatically generated antigen receptors.
- Orlando B. Giorgetti
- , Connor P. O’Meara
- & Thomas Boehm
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Article
| Open Access
In situ tumour arrays reveal early environmental control of cancer immunity
Skin tumour array by microporation (STAMP) captures the dynamic relationships of spatial, cellular and molecular components of tumour rejection and has the potential to translate therapeutic concepts into successful clinical strategies.
- Guadalupe Ortiz-Muñoz
- , Markus Brown
- & Christine Moussion
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SARS-CoV-2 Omicron boosting induces de novo B cell response in humans
COVID-19 booster immunizations aimed at spike protein from new SARS-CoV-2 variants induce robust germinal centre B cell responses against the original spike protein, as well as de novo B cell responses against the variant spike protein.
- Wafaa B. Alsoussi
- , Sameer Kumar Malladi
- & Ali H. Ellebedy
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Immunoglobulin M perception by FcμR
The structural basis for the molecular mechanism of recognition of different IgM forms by the IgM receptor FcμR is determined using crystallography and cryo-electron microscopy.
- Yaxin Li
- , Hao Shen
- & Junyu Xiao
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Article
| Open Access
The dietary sweetener sucralose is a negative modulator of T cell-mediated responses
Consumption of high doses of the sweetener sucralose has immunomodulatory effects in mice, as a result of reduced T cell proliferation and differentiation.
- Fabio Zani
- , Julianna Blagih
- & Karen H. Vousden
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Autoimmunity in Down’s syndrome via cytokines, CD4 T cells and CD11c+ B cells
An autoimmune-prone state of steady-state cytokinopathy, hyperactivated CD4 T cells and ongoing B cell activation contributes to a breach in immune tolerance in individuals with Down’s syndrome.
- Louise Malle
- , Roosheel S. Patel
- & Dusan Bogunovic
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Matters Arising |
Reply to: GOT1 constrains TH17 cell differentiation, while promoting iTreg cell differentiation
- Tao Xu
- , Zhen Qin
- & Sheng Ding
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Tissue CD14+CD8+ T cells reprogrammed by myeloid cells and modulated by LPS
Bacterial products in the gut–liver axis and tissue stromal factors can tune liver immunity by driving myeloid instruction of CD8+ T cells with immunomodulatory ability.
- Laura J. Pallett
- , Leo Swadling
- & Mala K. Maini
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Functional T cells are capable of supernumerary cell division and longevity
Through iterative cycles of viral challenge and rechallenge over ten years, mouse T cells are demonstrated to have essentially infinite potential for population expansion and longevity without malignant transformation or loss of functional competence.
- Andrew G. Soerens
- , Marco Künzli
- & David Masopust
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Molecular fate-mapping of serum antibody responses to repeat immunization
Serum antibody responses to sequential homologous booster vaccines derive overwhelmingly from primary cohort B cells at the expense of de novo responses; this ‘primary addiction’ can be overcome by boosting with variant antigens.
- Ariën Schiepers
- , Marije F. L. van ’t Wout
- & Gabriel D. Victora
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Article
| Open Access
Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution
Convergent mutations in hotspots of the SARS-CoV-2 Omicron receptor-binding domain can cause immune evasion and maintain sufficient ACE2-binding capability.
- Yunlong Cao
- , Fanchong Jian
- & Xiaoliang Sunney Xie
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Article
| Open Access
Antibody feedback regulates immune memory after SARS-CoV-2 mRNA vaccination
Pre-existing high-affinity antibodies alter germinal centre and memory B cell selection by lowering the activation threshold for B cells and through direct masking of their cognate epitopes, thereby permitting a diverse set of abundant lower-affinity clones targeting alternate epitopes to participate in the immune response.
- Dennis Schaefer-Babajew
- , Zijun Wang
- & Michel C. Nussenzweig
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Article
| Open Access
Dendritic cells direct circadian anti-tumour immune responses
Rhythmic trafficking of dendritic cells to the tumour draining lymph node governs a circadian response of tumour-antigen-specific CD8+ T cells that is dependent on the circadian expression of the co-stimulatory molecule CD80.
- Chen Wang
- , Coline Barnoud
- & Christoph Scheiermann
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Article
| Open Access
Functional antibodies exhibit light chain coherence
Among naturally occurring antibodies that have adapted to antigen, those with similar heavy chains usually have similar light chains.
- David B. Jaffe
- , Payam Shahi
- & Wyatt J. McDonnell
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PD-1 combination therapy with IL-2 modifies CD8+ T cell exhaustion program
PD-1+TCF1+ stem-like CD8+ T cells—precursors of exhausted CD8+ T cells—are not fate-locked into the exhaustion program; their differentiation trajectory can be changed by IL-2 signals.
- Masao Hashimoto
- , Koichi Araki
- & Rafi Ahmed
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An LKB1–mitochondria axis controls TH17 effector function
OPA1 regulates the formation of the distinct mitochondrial morphology observed in T helper 17 cells, which influences cytokine expression via LKB1.
- Francesc Baixauli
- , Klara Piletic
- & Erika L. Pearce
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Long-primed germinal centres with enduring affinity maturation and clonal migration
Using HIV Env protein immunogen priming in rhesus monkeys followed by a long period without further immunization, we demonstrate germinal centre B cells lasting at least 6 months, showing promise in regard to difficult vaccine targets.
- Jeong Hyun Lee
- , Henry J. Sutton
- & Shane Crotty
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Article
| Open Access
Novel antigen-presenting cell imparts Treg-dependent tolerance to gut microbiota
Single-cell transcriptomic and epigenetic analysis has enabled the identification of Thetis cells, a class of RORγt+ antigen-presenting cells with a key role in the differentiation of commensal microbiota-induced peripheral regulatory T cells.
- Blossom Akagbosu
- , Zakieh Tayyebi
- & Chrysothemis C. Brown
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Article
| Open Access
Dysregulated naive B cells and de novo autoreactivity in severe COVID-19
Single-cell B cell repertoire analysis identifies the expansion of a naive-derived population of antibody-secreting cells contributing to de novo autoreactivity in patients with severe COVID-19 and those with post-COVID symptoms.
- Matthew C. Woodruff
- , Richard P. Ramonell
- & Ignacio Sanz
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Article |
cBAF complex components and MYC cooperate early in CD8+ T cell fate
cBAF is a negative determinant of memory T cell fate and the manipulation of cBAF early in T cell differentiation can improve cancer immunotherapy.
- Ao Guo
- , Hongling Huang
- & Douglas R. Green
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Article
| Open Access
BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection
Biochemical and structural studies of the interactions between antibodies and spike proteins from SARS-CoV-2 Omicron subvariants indicate how these variants have evolved to escape antibody-mediated neutralization.
- Yunlong Cao
- , Ayijiang Yisimayi
- & Xiaoliang Sunney Xie
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Pregnancy enables antibody protection against intracellular infection
Pregnancy-induced post-translational antibody modification enables protection against the prototypical intracellular pathogen Listeria monocytogenes.
- John J. Erickson
- , Stephanie Archer-Hartmann
- & Sing Sing Way
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Article
| Open Access
Extricating human tumour immune alterations from tissue inflammation
Complementary single-cell approaches show that a population of regulatory T cells co-expressing ICOS and IL-1 receptor type 1 is highly enriched in tumours but not in site-matched inflamed non-malignant tissue.
- Florian Mair
- , Jami R. Erickson
- & Martin Prlic
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Article
| Open Access
TLR7 gain-of-function genetic variation causes human lupus
The missense TLR7Y264H gain-of-function genetic variation causes systemic lupus erythematosus in humans and mice.
- Grant J. Brown
- , Pablo F. Cañete
- & Carola G. Vinuesa
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Article
| Open Access
Increased memory B cell potency and breadth after a SARS-CoV-2 mRNA boost
A third dose of an mRNA vaccine against SARS-CoV-2 results in an expanded B cell repertoire that produces antibodies with increased potency and breadth.
- Frauke Muecksch
- , Zijun Wang
- & Michel C. Nussenzweig
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Obesity alters pathology and treatment response in inflammatory disease
Obesity changes the characteristics of the immune response induced in a mouse model of atopic dermatitis, suggesting therapies that could be used against immune dysregulation in obesity.
- Sagar P. Bapat
- , Caroline Whitty
- & Alexander Marson
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Establishment of fetomaternal tolerance through glycan-mediated B cell suppression
Pathways of glycan-mediated B cell suppression during pregnancy are important for promoting fetomaternal tolerance.
- G. Rizzuto
- , J. F. Brooks
- & A. Erlebacher
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Germinal centre-driven maturation of B cell response to mRNA vaccination
Sequencing of B cell receptors and expression of the corresponding monoclonal antibodies is used to characterize the evolution of the long-term B cell response to SARS-CoV-2 mRNA vaccination.
- Wooseob Kim
- , Julian Q. Zhou
- & Ali H. Ellebedy
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Article
| Open Access
T cell responses to SARS-CoV-2 spike cross-recognize Omicron
T cell responses to spike protein from the SARS-CoV-2 Omicron variant (B.1.1.529) are broadly similar to the responses to ancestral, Beta (B.1.351) and Delta (B.1.617.2) spike protein in vaccinated, infected and unvaccinated individuals.
- Roanne Keeton
- , Marius B. Tincho
- & Catherine Riou
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Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM
The identification of high-affinity molecular mimicry between the Epstein–Barr virus (EBV) transcription factor EBNA1 and the CNS protein GlialCAM provides a mechanistic link between multiple sclerosis and EBV.
- Tobias V. Lanz
- , R. Camille Brewer
- & William H. Robinson
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Article
| Open Access
Broadly neutralizing antibodies target a haemagglutinin anchor epitope
A distinct class of broadly neutralizing antibodies to the influenza virus target a membrane-proximal anchor epitope of the haemagglutinin stalk domain.
- Jenna J. Guthmiller
- , Julianna Han
- & Patrick C. Wilson
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Considerable escape of SARS-CoV-2 Omicron to antibody neutralization
An isolate of the Omicron variant of SARS-COV-2 was completely or partially resistant to neutralization by all nine clinically approved monoclonal antibodies tested.
- Delphine Planas
- , Nell Saunders
- & Olivier Schwartz
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Article
| Open Access
Signature of long-lived memory CD8+ T cells in acute SARS-CoV-2 infection
Evidence of a transcriptional signature that marks precursors of long-lived CD8+ memory T cells in SARS-CoV-2 infection.
- Sarah Adamo
- , Jan Michler
- & Onur Boyman
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Fam72a enforces error-prone DNA repair during antibody diversification
FAM72A interacts with UNG2 to regulate the balance between error-prone and error-free DNA repair.
- Mélanie Rogier
- , Jacques Moritz
- & Bernardo Reina-San-Martin
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FAM72A antagonizes UNG2 to promote mutagenic repair during antibody maturation
FAM72A differentially controls mutation rates by regulating uracil processing at different stages of the cell cycle, thereby regulating somatic hypermutation and class-switch recombination in B cells.
- Yuqing Feng
- , Conglei Li
- & Alberto Martin
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Article
| Open Access
Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2
Seronegative healthcare workers with an innate signature of infection preferentially expand pre-existing T cells targeting the conserved replication transcription complex of SARS-CoV-2 in abortive infection.
- Leo Swadling
- , Mariana O. Diniz
- & Mala K. Maini
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Parallelism of intestinal secretory IgA shapes functional microbial fitness
The functional role of intestinal secretory IgA for host–microbiota interactions is investigated, showing that intestinal bacterial exposure leads to selection of diverse plasma cells that secrete antigen-specific IgA, which predominantly targets bacterial membranes.
- Tim Rollenske
- , Sophie Burkhalter
- & Andrew J. Macpherson
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Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity
Immune analyses against circulating SARS-CoV-2 variants show that mRNA vaccination induces robust neutralizing antibodies and boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection.
- Carolina Lucas
- , Chantal B. F. Vogels
- & Akiko Iwasaki
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Article
| Open Access
Anti-SARS-CoV-2 receptor-binding domain antibody evolution after mRNA vaccination
Individual memory antibodies selected over time by natural infection with SARS-CoV-2 have greater potency and breadth than antibodies elicited by vaccination, whereas the overall neutralizing potency of plasma is greater following vaccination.
- Alice Cho
- , Frauke Muecksch
- & Michel C. Nussenzweig
