Featured
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Article
| Open Access
Targeting of intracellular oncoproteins with peptide-centric CARs
Peptide-centric chimeric antigen receptors (PC-CARs) provide a platform to address the challenges involved in targeting intracellular oncoproteins, and PC-CARs based on the neuroblastoma-dependency gene PHOX2B induce elimination of aggressive tumors.
- Mark Yarmarkovich
- , Quinlen F. Marshall
- & John M. Maris
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Article
| Open Access
A common allele of HLA is associated with asymptomatic SARS-CoV-2 infection
The human leukocyte antigen allele HLA-B*15:01 is associated with asymptomatic SARS-CoV-2 infection due to pre-existing T cell immunity.
- Danillo G. Augusto
- , Lawton D. Murdolo
- & Jill A. Hollenbach
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Article
| Open Access
γδ T cells are effectors of immunotherapy in cancers with HLA class I defects
γδ T cells contribute to the response to immune checkpoint blockade treatment in patients with HLA-class-I-negative DNA mismatch repair-deficient colon cancers. .
- Natasja L. de Vries
- , Joris van de Haar
- & Emile E. Voest
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Article |
A RORγt+ cell instructs gut microbiota-specific Treg cell differentiation
Induction of T regulatory cells by gut microbes is mediated by antigen-presenting RORγt+ cells, unlike that of T follicular helper and T helper 17 cells, which requires different cell types.
- Ranit Kedmi
- , Tariq A. Najar
- & Dan R. Littman
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Article |
Deciphering the immunopeptidome in vivo reveals new tumour antigens
A newly developed genetically engineered mouse model enables the analysis of specific antigen presentation in vivo, providing insights into the tumour immunopeptidome and cancer progression.
- Alex M. Jaeger
- , Lauren E. Stopfer
- & Tyler Jacks
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Article
| Open Access
RETRACTED ARTICLE: Cross-HLA targeting of intracellular oncoproteins with peptide-centric CARs
Targeting peptides from unmutated cancer drivers that are expressed in tumours but not in normal tissues using peptide-centric chimeric antigen receptors shows potential as treatment for cancer.
- Mark Yarmarkovich
- , Quinlen F. Marshall
- & John M. Maris
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Letter |
Pancreatic islets communicate with lymphoid tissues via exocytosis of insulin peptides
A sensitive T cell tracking assay reveals immunogenic activity of specific catabolized peptide fragments of insulin and their effects on T cell activity in lymph nodes, highlighting communication between pancreatic islets and lymphoid tissue.
- Xiaoxiao Wan
- , Bernd H. Zinselmeyer
- & Emil R. Unanue
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Letter |
Hippo/Mst signalling couples metabolic state and immune function of CD8α+ dendritic cells
A data-driven analysis helps to identify specific roles of the Hippo signalling kinases Mst1 and Mst2 in integrating metabolic activity and cytokine signalling in dendritic cells, and thereby orchestrating immune cell function.
- Xingrong Du
- , Jing Wen
- & Hongbo Chi
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Letter |
Structure of the human MHC-I peptide-loading complex
Electron cryo-microscopy structures of the human peptide-loading complex shed light on its operation and on the onset of adaptive immune responses.
- Andreas Blees
- , Dovile Januliene
- & Robert Tampé
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Letter |
Antigen presentation profiling reveals recognition of lymphoma immunoglobulin neoantigens
Evidence for the abundant presentation of class II neoantigens by a human B-cell lymphoma.
- Michael S. Khodadoust
- , Niclas Olsson
- & Ash A. Alizadeh
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Letter |
T-cell activation by transitory neo-antigens derived from distinct microbial pathways
Activation of mucosal-associated invariant T (MAIT) cells is shown to require key genes encoding an early intermediate in bacterial riboflavin synthesis, 5-amino-6-d-ribitylaminouracil; this reacts non-enzymatically with metabolites to form short-lived antigens that are captured and stabilized by MR1 for presentation to MAIT cells.
- Alexandra J. Corbett
- , Sidonia B. G. Eckle
- & James McCluskey
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Letter |
Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria
Group 3 innate lymphoid cells are shown to process and present antigen and to control CD4+ T-cell responses to intestinal commensal bacteria through an MHC-class-II-dependent mechanism.
- Matthew R. Hepworth
- , Laurel A. Monticelli
- & Gregory F. Sonnenberg
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News & Views |
Vitamins prime immunity
The finding that derivatives of vitamin B can bind to an antigen-presenting protein that stimulates specialized immune cells suggests a novel mechanism by which the immune system detects microbial infections. See Article p.717
- Wei-Jen Chua
- & Ted H. Hansen
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Article |
MR1 presents microbial vitamin B metabolites to MAIT cells
The structure of the major histocompatibility complex (MHC)-class-I-like molecule MR1 in complex with a vitamin B9 derivative is determined; metabolites of vitamin B2 are shown to activate MR1-restricted mucosal-associated invariant T cells, implicating them in microbial immunosurveillance.
- Lars Kjer-Nielsen
- , Onisha Patel
- & James McCluskey
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Letter |
Killer cell immunoglobulin-like receptor 3DL1-mediated recognition of human leukocyte antigen B
- Julian P. Vivian
- , Renee C. Duncan
- & Jamie Rossjohn
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News |
Cod genome reveals unusual immune system
Missing molecules show evolutionary flexibility, and may help fish farmers.
- George Wigmore
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Letter |
MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers
Using whole-transcriptome sequencing, this paper identifies recurrent gene translocations in B-cell lymphomas that involve the MHC class II transactivator CIITA. These translocations lead to downregulation of cell surface HLA class II expression and, in the case of some fusion partners, overexpression of CD274/CD273 ligands, which have the potential to reduce the antitumour response against these lymphomas.
- Christian Steidl
- , Sohrab P. Shah
- & Randy D. Gascoyne
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Letter |
Microenvironmental reprogramming of thymic epithelial cells to skin multipotent stem cells
The thymus contains thymic epithelial cells (TECs), which form a complex three-dimensional network organized into cortical and medullary compartments. It is shown here that these cells are plastic. Clonogenic TECs can acquire new properties when exposed to the skin microenvironment; under such conditions, they can permanently adopt the fate of hair follicle multipotent stem cells. Hence, microenvironmental cues can be sufficient to re-direct epithelial cell fate.
- Paola Bonfanti
- , Stéphanie Claudinot
- & Yann Barrandon
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Letter |
Effects of thymic selection of the T-cell repertoire on HLA class I-associated control of HIV infection
'Elite controllers' are rare people who are infected with HIV but maintain low levels of HIV RNA without being treated, making it unlikely that they will develop AIDS. Certain HLA class I alleles, notably HLA-B57, are enriched in elite controllers. Here a model is proposed to explain how such elite controllers generate an effective immune response against HIV. In this model, HLA-B57 binds to fewer self-peptides, resulting in a T-cell repertoire with enhanced cross-reactivity and leading to a more effective T-cell response to the virus.
- Andrej Košmrlj
- , Elizabeth L. Read
- & Arup K. Chakraborty
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Letter |
The kinetics of two-dimensional TCR and pMHC interactions determine T-cell responsiveness
Quantification of the interaction of T-cell receptors with their peptide–MHC ligands in two–dimensional membranes is shown to yield larger dissociation rate constants than previous assays where one of the interacting partners was in solution.
- Jun Huang
- , Veronika I. Zarnitsyna
- & Cheng Zhu
Epithelial IFNγ signalling and compartmentalized antigen presentation orchestrate gut immunity