Featured
-
-
Article
| Open AccessMyeloid apolipoprotein E controls dendritic cell antigen presentation and T cell activation
Cholesterol homeostasis can modulate immunity via multiple pathways. Here the authors show that apolipoprotein E, an important regulator of cholesterol, produced by myeloid cells can regulate T cell activation by controlling the antigen presentation activity of dendritic cells in both humans and mice.
- Fabrizia Bonacina
- , David Coe
- & Giuseppe D. Norata
-
Article
| Open AccessA novel probe to assess cytosolic entry of exogenous proteins
The mechanism of protein dislocation into the cytosol during antigen cross-presentation is poorly understood. Here the authors engineer a dislocation reporter fusing a glycosylated luciferase variant to the Fc region of IgG1, and find that dislocation is the rate limiting step in cross-presentation.
- Qiao Lu
- , Jeff E. Grotzke
- & Peter Cresswell
-
Article
| Open AccessNonstimulatory peptide–MHC enhances human T-cell antigen-specific responses by amplifying proximal TCR signaling
Coagonism, the ability of nonstimulatory antigens to promote T-cell activation, has been reported in mice. Here the authors show that coagonism also occurs in human CD8 T cells, in which a nonstimulatory HIV GAG peptide enhances a specific T-cell response to a hepatitis B virus epitope by amplifying T-cell receptor signals.
- Xiang Zhao
- , Shvetha Sankaran
- & Nicholas R. J. Gascoigne
-
Article
| Open AccessHuman in vivo-generated monocyte-derived dendritic cells and macrophages cross-present antigens through a vacuolar pathway
Cross-presentation, or the presentation of exogenous antigens on MHC-I, is thought to be restricted to dendritic cells (DCs). Here the authors show that human DCs and macrophages developed in vivo from monocytes can both perform cross-presentation using a non-conventional pathway, but only DCs are capable of inducing cytotoxic CD8+ T cells.
- Tsing-Lee Tang-Huau
- , Paul Gueguen
- & Elodie Segura
-
Article
| Open AccessLymphotoxin α fine-tunes T cell clonal deletion by regulating thymic entry of antigen-presenting cells
Autoreactive T cells are removed during their development in the thymus through the functions of medullary thymic epithelial cells (mTEC) and dendritic cells (DC), a process termed negative selection. Here the authors show that mTEC-T cell crosstalk and lymphotoxin α signalling are essential for the proper recruitment of DCs into the thymus.
- Noëlla Lopes
- , Jonathan Charaix
- & Magali Irla
-
Article
| Open AccessDivergent T-cell receptor recognition modes of a HLA-I restricted extended tumour-associated peptide
Human leukocyte antigen (HLA) presents peptides to activate T cells, but many aspects in the T cell receptor (TCR)/HLA interaction remain unclear. Here the authors show, via structural data, that two TCRs differentially recognize the same tumour peptide/HLA complex and induce contrasting conformation changes of the peptide.
- Kok Fei Chan
- , Benjamin S. Gully
- & Jamie Rossjohn
-
Article
| Open AccessCancer-associated fibroblasts induce antigen-specific deletion of CD8 + T Cells to protect tumour cells
Tumours employ a variety of strategies to induce immune suppression. Here the authors show that cancer-associated fibroblasts process and cross-present tumour-antigens to T-cells resulting in antigen-specific T cell death and dysfunction via upregulation of both cell death and immune checkpoint signals.
- Matthew A. Lakins
- , Ehsan Ghorani
- & Jacqueline D. Shields
-
Article
| Open AccessEffector CD4+ T cells recognize intravascular antigen presented by patrolling monocytes
Monocytes constitutively adhere and crawl along the glomerular endothelium and are thought to contribute to glomerulonephritis. Here the authors use multiphoton microscopy to show local antigen presentation by MHCII+ monocytes to T cells in glomerular capillaries of mice.
- Clare L. V. Westhorpe
- , M. Ursula Norman
- & Michael J. Hickey
-
Article
| Open AccessCD1d-dependent immune suppression mediated by regulatory B cells through modulations of iNKT cells
Regulatory B cells (Breg) are known to suppress immune responses by secreting interleukin-10 (IL-10). Here the authors show that, alternatively, Bregs may also present lipid antigens on surface CD1d to induce IFN-γ production from invariant natural killer cells to ameliorate experimental arthritis via IL-10-independent pathways.
- K. Oleinika
- , E. C. Rosser
- & C. Mauri
-
Article
| Open AccessNon-equivalent antigen presenting capabilities of dendritic cells and macrophages in generating brain-infiltrating CD8 + T cell responses
Dendritic cell antigen presentation is central to CD8+ T cell responses, but surprisingly little is known about the requirement for this functionality in the central nervous system. Here, the authors use three different models of neuroinflammation to show the importance of these cells in the CNS and in response to cerebral malaria, picornavirus infection and experimental glioma.
- Courtney S. Malo
- , Matthew A. Huggins
- & Aaron J. Johnson
-
Article
| Open AccessT cells specific for post-translational modifications escape intrathymic tolerance induction
Post-translational modifications are associated with autoimmune diseases but definitive evidence of their contribution to escape from central tolerance mechanisms is needed. Here, the authors show that T cells specific for post-translational modifications of type II collagen escape intrathymic tolerance induction in a mouse model of rheumatoid arthritis.
- Bruno Raposo
- , Patrick Merky
- & Johan Bäcklund
-
Article
| Open AccessLipid bodies containing oxidatively truncated lipids block antigen cross-presentation by dendritic cells in cancer
Tumor-associated dendritic cells are defective in their ability to cross-present antigens, and they accumulate lipid bodies. Here the authors show that this defect is due to an impaired trafficking of peptide-MHC class I caused by the interaction of electrophilic lipids with chaperone heat shock protein 70.
- Filippo Veglia
- , Vladimir A. Tyurin
- & Dmitry I. Gabrilovich
-
Article
| Open AccessMigratory dendritic cells acquire and present lymphatic endothelial cell-archived antigens during lymph node contraction
Viral infection and vaccination both induce lasting persistence of antigens for protective responses. Here the authors show that migratory dendritic cells, independent of the transcription factor BatF3 for their development, contribute to “archived antigen” exchange with lymphatic endothelial cells.
- Ross M. Kedl
- , Robin S. Lindsay
- & Beth A. Jirón Tamburini
-
Article
| Open AccessSTIM1 promotes migration, phagosomal maturation and antigen cross-presentation in dendritic cells
STIM proteins sense Ca2+ depletion in the ER and activate store-operated Ca2+-entry (SOCE) in response, a process associated with dendritic cell functions. Here the authors show STIM1 is the major isoform controlling SOCE in mouse dendritic cells and provide a mechanism for its requirement in antigen cross-presentation.
- Paula Nunes-Hasler
- , Sophia Maschalidi
- & Nicolas Demaurex
-
Article
| Open AccessUNC93B1 interacts with the calcium sensor STIM1 for efficient antigen cross-presentation in dendritic cells
STIM proteins sense Ca2+ depletion in the ER and activate store-operated Ca2+ entry in response, a process associated with dendritic cell (DC) functions. Here, the authors show that optimal antigen cross-presentation in DCs requires the association of the chaperone molecule UNC93B1 with STIM1.
- Sophia Maschalidi
- , Paula Nunes-Hasler
- & Bénédicte Manoury
-
Article
| Open AccessAdipocyte adaptive immunity mediates diet-induced adipose inflammation and insulin resistance by decreasing adipose Treg cells
Obesity is associated with inflammation in adipose tissue, characterized by a shift in local T cell subsets. Here the authors show that loss of MHCII expression on adipocytes increases levels of immunosuppressive regulatory T cells in adipose tissue, which enhances insulin sensitivity.
- Tuo Deng
- , Joey Liu
- & Willa A. Hsueh
-
Article
| Open AccessStructural and regulatory diversity shape HLA-C protein expression levels
HLA-C expression levels correlate with immune responses to pathogens and autoimmunity, and vary in an allele-specific manner across individuals. Here the authors identify factors that drive differential expression of HLA-C allomorphs at the cell surface, and influence the structure of the peptide-binding cleft and diversity of peptides bound by HLA-C molecules.
- Gurman Kaur
- , Stephanie Gras
- & Lars Fugger
-
Article
| Open AccessDifferent populations of CD11b+ dendritic cells drive Th2 responses in the small intestine and colon
T helper 2 (Th2) cell responses are essential for immunity against parasites, but how Th2 response is modulated in the gut is still unclear. Here the authors show that distinct dendritic cell subsets distinguishable by CD11b, CD103 and IRF4 function in the small intestine or colon to promote Th2 responses.
- Johannes U. Mayer
- , Mimoza Demiri
- & Simon W. Milling
-
Article
| Open AccessThe ATP-binding cassette transporter A1 regulates phosphoantigen release and Vγ9Vδ2 T cell activation by dendritic cells
γδT cells are activated by phosphoantigens, and ABCA1 is involved in cholesterol transport. Here the authors link these ideas to show that ABCA1, apoA-I and BTN3A1 regulate extracellular phosphoantigen release by dendritic cells, and implicate ABCA1 in mevalonate-mediated activation of Vγ9Vδ2 T cells.
- Barbara Castella
- , Joanna Kopecka
- & Massimo Massaia
-
Article
| Open AccessHSPs drive dichotomous T-cell immune responses via DNA methylome remodelling in antigen presenting cells
Low dose of the heat shock protein gp96 can drive effector T-cell responses, yet high-dose gp96 is immunosuppressive by expanding the regulatory T-cell population. Here the authors explain this dichotomy by showing that high-dose gp96 can drive plasmacytoid dendritic cell expression of neuropilin-1, thus functionally supporting interaction with Treg cells.
- Lauren B. Kinner-Bibeau
- , Abigail L. Sedlacek
- & Robert J. Binder
-
Article
| Open AccessHLA-DP84Gly constitutively presents endogenous peptides generated by the class I antigen processing pathway
MHC class I and II molecules generally present endogenous and exogenous peptides, respectively, through distinct mechanisms. Here, the authors show that the class II molecule HLA-DP84Glyuses both class I and II mechanisms to constitutively present peptides.
- Yuki Yamashita
- , Mark Anczurowski
- & Naoto Hirano
-
Article
| Open AccessCognate antigen engagement on parenchymal cells stimulates CD8+ T cell proliferation in situ
Professional antigen presenting cells (APC) are the major activator of T cells that then hone to sites of inflammation. Using islet cell grafts, here the authors show that parenchymal cells can present antigen to activate CD8+T cells at inflammatory sites, coining this a ‘mezzanine response’ distinct from primary and secondary responses associated with professional APCs.
- Robyn M. Sutherland
- , Sarah L. Londrigan
- & Andrew M. Lew
-
Article
| Open AccessStabilizing short-lived Schiff base derivatives of 5-aminouracils that activate mucosal-associated invariant T cells
MAIT cells are activated by MR1 restricted antigens derived from riboflavin biosynthesis. Here the authors characterize MAIT cell antigenicity and synthesize a water stable antigen that activates human MAIT cellsin vitro and mouse MAIT cells in vivo.
- Jeffrey Y. W. Mak
- , Weijun Xu
- & David P. Fairlie
-
Article
| Open AccessCD45-mediated control of TCR tuning in naïve and memory CD8+ T cells
Naïve T cells establish self-tolerance via negative selection of cells with strong reactivity for self-peptide/MHC complexes, but undergo T-cell receptor (TCR) desensitisation when leaving the thymus. Here, Choet al.show that TCR desensitisation correlates with cell-surface density of the phosphatase CD45.
- Jae-Ho Cho
- , Hee-Ok Kim
- & Jonathan Sprent
-
Article
| Open AccessMHC class II complexes sample intermediate states along the peptide exchange pathway
MHCII proteins bind and present both foreign and self-antigens to potentially activate CD4+ T cells via cognate T cell receptors (TCRs) during the adaptive immune response. Here, the authors combine NMR-detected H/D exchange with Markov modelling analysis to shed light on the dynamics of MHCII peptide exchange.
- Marek Wieczorek
- , Jana Sticht
- & Christian Freund
-
Article
| Open AccessSaponin-based adjuvants induce cross-presentation in dendritic cells by intracellular lipid body formation
Saponin-based adjuvants are being explored as vaccine components as they induce high levels of antigen cross-presentation, but it is unknown how. Here the authors show that these adjuvants enhance cross-presentation by driving production of lipid bodies inside CD11b dendritic cells.
- Martijn H. den Brok
- , Christian Büll
- & Gosse J. Adema
-
Article
| Open AccessT cell receptor recognition of CD1b presenting a mycobacterial glycolipid
Germline-encoded mycolyl lipid-reactive (GEM) T cells recognize CD1b proteins presenting mycobacterial mycolates via their T-cell receptors (TCRs). Here, the authors present the structure of this interaction and provide a molecular basis for the co-recognition of CD1b and a mycobacterial glycolipid.
- Stephanie Gras
- , Ildiko Van Rhijn
- & Jamie Rossjohn
-
Article
| Open AccessEfficient generation of monoclonal antibodies against peptide in the context of MHCII using magnetic enrichment
Generating antibodies specific for the peptide–MHCII complexes has been challenging, with only a handful made to date. Here, the authors develop a more efficient approach to generate these antibodies, and demonstrate their potential in research and therapeutic applications.
- Justin A. Spanier
- , Daniel R. Frederick
- & Brian T. Fife
-
Article
| Open AccessIncreased generation of Foxp3+ regulatory T cells by manipulating antigen presentation in the thymus
The degree of Treg self-antigen reactivity varies across experimental systems. Here the authors develop a new model of skin autoimmunity and show that the size of tissue-specific Treg pool in the thymus depends on AIRE, the availability of the tissue antigen, and its presentation by dendritic cells.
- Jiqiang Lin
- , Lu Yang
- & Juan J. Lafaille
-
Article
| Open AccessMelanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy
Immunotherapy is used to treat melanoma, however patient responses vary widely highlighting the need for factors that can predict therapeutic success. Here, the authors show that MHC-II molecules expressed by tumour cells are positively correlated with a good response to therapy and overall patient survival.
- Douglas B. Johnson
- , Monica V. Estrada
- & Justin M. Balko
-
Article
| Open AccessCrystal structure of the N-myristoylated lipopeptide-bound MHC class I complex
Lipid antigens have been added to the antigenic repertoire in recent years. Here, the authors have identified Mamu-B*098 as a lipopeptide antigen presenting molecule and using structural and biochemical analysis have shown that it has a different antigen binding pocket to previously analysed proteins.
- Daisuke Morita
- , Yukie Yamamoto
- & Masahiko Sugita
-
Article
| Open AccessGlobal proteogenomic analysis of human MHC class I-associated peptides derived from non-canonical reading frames
Cryptic translation of the 'non-coding' genome is increasingly recognised, however its biological significance remains unclear. Laumont et al.employ proteogenomic techniques to map the human immunoproteome, and find that approximately 10% of MHC class I-associated peptides are cryptic.
- Céline M. Laumont
- , Tariq Daouda
- & Claude Perreault
-
Article
| Open AccessIdentification and characterization of latency-associated peptide-expressing γδ T cells
Latency-associated peptide (LAP) is a membrane-bound form of TGF-β1. Here the authors show that LAP marks a subset of regulatory γδ T cells with innate gut-homing properties, which present antigen and induce CD4+ Foxp3+ in Peyer's patches and lamina propria.
- Rafael M. Rezende
- , Andre P. da Cunha
- & Howard L. Weiner
-
Article
| Open AccessMHC variation sculpts individualized microbial communities that control susceptibility to enteric infection
Composition of the gut microbiota is regulated by IgA antibodies which are produced under the control of MHCII-restricted B cells. Here the authors show that MHCII polymorphisms sculpt bacterial composition of the gut, which influences a host’s susceptibility to enteric Salmonellainfection.
- Jason L. Kubinak
- , W. Zac Stephens
- & June L. Round
-
Article |
Ligand-engaged TCR is triggered by Lck not associated with CD8 coreceptor
The early signalling events that trigger initial T-cell receptor signalling are not clearly defined. Here the authors show that this occurs in two stages, the first between the CD8 coreceptor and CD3 requiring Lck association to CD8, while the second interaction requires binding of major histocompatibility molecules.
- Javier Casas
- , Joanna Brzostek
- & Nicholas R. J. Gascoigne
-
Article |
Divergent paths for the selection of immunodominant epitopes from distinct antigenic sources
Whether antigen processing and presentation differs between pathogen-derived antigens and self-antigens is not clear. Here the authors use a reductionist cell-free approach to study antigen processing, uncovering differences in antigen sensitivity to digestion by cathepsins and resistance to DM.
- AeRyon Kim
- , Isamu Z. Hartman
- & Scheherazade Sadegh-Nasseri
-
Article |
MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration
MHC-I is expressed in neurons where it is implicated in synaptic plasticity and neuron regeneration. Here, Cebrián et al. report an increase in MHC-I expression in brain neurons from Parkinson’s disease patients, which is triggered by microglial activation and circulating dopamine.
- Carolina Cebrián
- , Fabio A. Zucca
- & David Sulzer
-
Article
| Open AccessImpact of genomic polymorphisms on the repertoire of human MHC class I-associated peptides
Mass spectrometry (MS) has furthered our understanding of MHC class I-associated peptides (MIPs), but the technique is inadequate for studying MIP-associated polymorphisms. Here, the authors combine high-throughput MS with exome and transcriptome sequencing to identify polymorphic MIPs from two female siblings.
- Diana Paola Granados
- , Dev Sriranganadane
- & Claude Perreault
-
Article
| Open AccessMHC-dependent inhibition of uterine NK cells impedes fetal growth and decidual vascular remodelling
NK cells are involved in remodelling of the uterine vasculature during pregnancy and the extent of this process is influenced by the combination of maternal NK cell receptors and MHC-I of the fetus. Here, the authors provide further insights into how the presence of MHC-I from each parent differentially affects NK cell function.
- Jens Kieckbusch
- , Louise M. Gaynor
- & Francesco Colucci
-
Article
| Open Accessp53 increases MHC class I expression by upregulating the endoplasmic reticulum aminopeptidase ERAP1
The protein p53 is an important tumour suppressor. Here Wanget al.show that p53 can induce expression of MHC class I on the cell surface by promoting expression of the aminopeptidase ERAP1, and that this mechanism operates in cancer cells as well as those infected with influenza virus.
- Bei Wang
- , Dandan Niu
- & Ee Chee Ren
-
Article
| Open AccessExploring the MHC-peptide matrix of central tolerance in the human thymus
T cells learn to tolerate self-antigens in the thymus, where self-peptides are presented by thymic antigen-presenting cells. Here, the authors present an ex vivomass spectrometric analysis of the self-peptide repertoire associated with MHC I and II in human thymic tissue.
- Eleni Adamopoulou
- , Stefan Tenzer
- & Christina Stoeckle
-
Article |
The basis for limited specificity and MHC restriction in a T cell receptor interface
Although structural insights into antigen recognition by T cell receptors are increasingly available, the thermodynamic underpinnings are less well understood. Here the authors deconstruct the energetics of a representative interface and discover that peptide specificity, cross-reactivity and MHC restriction can be inextricably linked.
- Kurt H. Piepenbrink
- , Sydney J. Blevins
- & Brian M. Baker
-
Article
| Open AccessMouse urinary peptides provide a molecular basis for genotype discrimination by nasal sensory neurons
Major histocompatibility complex peptide ligands in mouse urine have been hypothesized to serve as signals for communication. In support of this hypothesis, Sturm and colleagues find that specific urinary peptides from genetically different mouse strains can be discriminated by nasal sensory neurons.
- Theo Sturm
- , Trese Leinders-Zufall
- & Hans-Georg Rammensee
-
Article |
Mst1 regulates integrin-dependent thymocyte trafficking and antigen recognition in the thymus
Autoreactive T cells are eliminated as they encounter self-antigens during transit through the thymus. Uedaet al. reveal that mice lacking the Hippo homologue Mst1 develop autoimmunity as a result of impaired integrin-dependent T cell migration through this negatively selective niche.
- Yoshihiro Ueda
- , Koko Katagiri
- & Tatsuo Kinashi
-
Article
| Open AccessRapid and adaptive evolution of MHC genes under parasite selection in experimental vertebrate populations
In vertebrates parasite-mediated selection is thought to maintain polymorphism in MHC genes where specific resistance MHC alleles increase under emerging selection. Here, experimental evidence is shown from six stickleback fish populations that varying parasite selection helps maintain MHC polymorphism.
- Christophe Eizaguirre
- , Tobias L. Lenz
- & Manfred Milinski
-
Article
| Open AccessStructure-based mutagenesis reveals the albumin-binding site of the neonatal Fc receptor
Albumin transport proteins circulate in the blood and are protected from degradation by interaction with the neonatal Fc receptor. Andersenet al. investigate the albumin binding site of the neonatal Fc receptor and find pH sensitive ionic networks at the binding interface.
- Jan Terje Andersen
- , Bjørn Dalhus
- & Inger Sandlie
-
Article
| Open AccessUnidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells
Exosomes released from cells can transfer RNA to recipient cells. In this study, the authors demonstrate that microRNAs in exosomes from T cells can be transferred to antigen-presenting cells during immune synapsis, and that this can alter gene expression, suggesting a new form of cellular communication.
- María Mittelbrunn
- , Cristina Gutiérrez-Vázquez
- & Francisco Sánchez-Madrid
-
Article |
The structure of superantigen complexed with TCR and MHC reveals novel insights into superantigenic T cell activation
Superantigens are bacterial toxins that interact with host immunoreceptors. Salineet al.report the X-ray structure of staphylococcal enterotoxin H in complex with its human receptors, MHC class II and the T-cell receptor, providing new insights into superantigenic T-cell activation.
- Maria Saline
- , Karin E. J. Rödström
- & Karin Lindkvist-Petersson