Antigen processing and presentation articles within Nature Communications

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  • Article
    | Open Access

    KRAS is commonly mutated at codon 12 in several cancer types, offering a unique opportunity for the development of neoantigen-targeted immunotherapy. Here the authors present a pipeline for the prediction, identification and validation of HLA class-I restricted mutant KRAS G12 peptides, leading to the generation of mutant KRAS-specific T cell receptors for adoptive T cell immunotherapy.

    • Adham S. Bear
    • , Tatiana Blanchard
    •  & Beatriz M. Carreno

  • Article
    | Open Access

    Tapasin is part of the peptide loading complex necessary for presenting antigenic peptides on MHC-I for the induction of adaptive immunity. Here the authors show that tapasin interacts with MHC-I in both conserved and allele-specific regions to promote antigen presentation, with tapasin L18 and K16 residues both implicated in this molecular interaction.

    • Huan Lan
    • , Esam T. Abualrous
    •  & Christian Freund

  • Article
    | Open Access

    Type II alveolar cells play central roles in multiple aspects of lung biology. Here the authors show that type II alveolar cells also constitutively express MHCII, exhibit limited MHCII antigen presentation capacity, and are a component of the host response to respiratory viral infection.

    • Sushila A. Toulmin
    • , Chaitali Bhadiadra
    •  & Laurence C. Eisenlohr

  • Article
    | Open Access

    The identification of HLA peptides by mass spectrometry is non-trivial. Here, the authors extended and used the wealth of data from the ProteomeTools project to improve the prediction of non-tryptic peptides using deep learning, and show their approach enables a variety of immunological discoveries.

    • Mathias Wilhelm
    • , Daniel P. Zolg
    •  & Bernhard Kuster

  • Article
    | Open Access

    Myosin II–mediated contractility is required for leukocyte migration. Here, authors show that lysosomes are involved in leukocyte migration by providing the platform where Ragulator complex interacts with the myosin phosphatase Rho-interacting protein (MPRIP) independently of mTORC1 and interferes with the interaction between MPRIP and a subunit of myosin light chain phosphatase (MLCP).

    • Takeshi Nakatani
    • , Kohei Tsujimoto
    •  & Atsushi Kumanogoh

  • Article
    | Open Access

    The molecular chaperones tapasin and TAPBPR play important roles in defining the repertoire of peptides displayed by MHC class I. Here, the authors combine NMR, ITC, fluorescence polarization measurements and deep mutational scanning analyses to reveal a peptide editing mechanism, where the G24-R36 loop in TAPBPR acts as a molecular trap to promote the selection of high-affinity peptide cargo.

    • Andrew C. McShan
    • , Christine A. Devlin
    •  & Nikolaos G. Sgourakis

  • Article
    | Open Access

    The immunology of Indigenous populations is generally understudied outside the context of diseases that are prevalent in these communities. Here the authors identify prevalence of influenza CD8+ T cell epitopes in an Indigenous Australian population expressing the susceptibility allomorph HLA A*24:02 and validate immunodominance of some of these epitopes in mice.

    • Luca Hensen
    • , Patricia T. Illing
    •  & Katherine Kedzierska

  • Article
    | Open Access

    Conventional T cell subsets are selected in the thymus by peptide bearing MHC expressed by cortical epithelial cells, in contrast cortical thymocytes express non-peptide bearing MHC molecules including CD1d and MR1 and select iNKT and MAIT cell populations respectively. Here, the authors generate a novel inducible MHC class-I trasnactivator murine system and suggest the absence of peptide-MHC on thymocytes is involved in the selection of non-peptide specific lymphocytes.

    • Hristo Georgiev
    • , Changwei Peng
    •  & Kristin A. Hogquist

  • Article
    | Open Access

    Type 2 conventional dendritic cells (cDC2) are important immune activators in adults, but their development and functions at the neonatal stage remain unclear. Here the authors show, using fate-mapping and single-cell RNA sequencing, that neonatal cDC2 come from multiple origins, but converge functionally as potent immune activators upon proper stimuli.

    • Nikos E. Papaioannou
    • , Natallia Salei
    •  & Barbara U. Schraml

  • Article
    | Open Access

    TARM1 is a LILR family member that drives cell signalling via interactions with FcRγ. Here the authors show that TARM1 binds collagens to activate dendritic cells and thereby is an effector of inflammatory arthritis, plus provide a soluble TARM-Fc fusion protein that can limit collagen-induced arthritis in mice.

    • Rikio Yabe
    • , Soo-Hyun Chung
    •  & Yoichiro Iwakura

  • Article
    | Open Access

    Thermostability of the peptide-MHC interaction is important for immunogenicity. Here the authors present a mass spectrometry method to measure thermostability among thousands of peptide-MHC complexes in parallel and a trained artificial neural network to predict immunogenenicity of cancer antigens.

    • Emma C. Jappe
    • , Christian Garde
    •  & Anthony W. Purcell

  • Article
    | Open Access

    B7-CD28 co-stimulation is important for T cell activation and clonal expansion in the periphery. Here the authors show that, in mouse thymus, B7-CD28 differentially controls thymocyte clonal deletion and Treg induction, with distinct CD28 signaling domains and B7-expressing antigen presenting cells mediating these two processes.

    • Masashi Watanabe
    • , Ying Lu
    •  & Richard J. Hodes

  • Article
    | Open Access

    Human endogenous retroviruses (HERV) normally remain quiescent, but can be reactivated by malignant transformation. Here the authors find, via HERV peptide library testing and tetramer validation, more profound HERV transcription and associated T cell recognition in myeloid cancer patients to implicate HERVs as potential therapeutic targets.

    • Sunil Kumar Saini
    • , Andreas Due Ørskov
    •  & Sine Reker Hadrup

  • Article
    | Open Access

    Antigen presenting cells induce CD4+ T helper (Th) differentiation upon pathogen encounters. Here the authors use fluorescently-labeled bacteria, helminth and fungi to track and describe the functions of IRF4+ migratory type 2 dendritic cells and monocytes in the specific induction of Th1, Th2 or Th17 responses following skin inoculation.

    • Kerry L. Hilligan
    • , Shiau-Choot Tang
    •  & Franca Ronchese

  • Article
    | Open Access

    Identifying peptides that can bind major histocompatibility complex II (MHC-II) is important for our understanding of T cell immunity and specificity. Here the authors present a yeast-display library screening approach that identifies more potential binders than various reported algorithms to help expand our understanding for antigen presentation.

    • C. Garrett Rappazzo
    • , Brooke D. Huisman
    •  & Michael E. Birnbaum

  • Article
    | Open Access

    T cell tolerance is established in the thymus via interactions with medullary thymic epithelial cells (mTEC) expressing tissue-restricted self antigens. Here, the authors suggest, using new transgenic mouse lines and single cell transcriptome analyses, that specific mTEC subsets are associated with distinct T cell fates.

    • Marie-Ève Lebel
    • , Marie Coutelier
    •  & Heather J. Melichar

  • Article
    | Open Access

    Immunopeptidomics allows identifying the cellular repertoire of MHC-bound peptides, but quantifying them remains challenging. Here, the authors present a method to efficiently generate internal peptide MHC standards and calibration curves, facilitating relative and absolute quantitative immunopeptidomics.

    • Lauren E. Stopfer
    • , Joshua M. Mesfin
    •  & Forest M. White

  • Article
    | Open Access

    Thymus is a unique environment hosting the development of many T cell subsets with distinct functions. Here the authors show that medullary thymic epithelial cells (mTEC) are functionally diverse, with LTβR signaling serving differential regulation of mTEC for specific control of multiple lineages of invariant natural killer T cells.

    • Beth Lucas
    • , Andrea J. White
    •  & Graham Anderson

  • Article
    | Open Access

    Murine ILCs can modulate T cell responses in MHCII-dependent manner. Here the authors show that human ILCs process and present antigens and induce T-cell responses upon exposure to IL-1-family cytokines; along with the article by Lehmann et al, this work elucidates how cytokines set context specificity of ILC-T cell crosstalk by regulating ILC antigen presentation.

    • Anna Rao
    • , Otto Strauss
    •  & Jenny Mjösberg

  • Article
    | Open Access

    Peptide-MHC (pMHC) tetramers are important tools for probing T cell repertoire and adaptive immune responses. Here the authors use a molecular chaperone, TAPBPR, to develop a high-throughput, multiplexible platform for pMHC tetramer generation to facilitate simultaneous assessments of T cell repertoire/antigen specificity and transcriptome.

    • Sarah A. Overall
    • , Jugmohit S. Toor
    •  & Nikolaos G. Sgourakis

  • Article
    | Open Access

    Kinesin-1 is a motor protein transporting cargo along microtubules. Here the authors show that kinesin-1 is required for antigen cross-presentation and coordinates endosome scission from early endosomes to allow sorting internalized cargoes towards the recycling endosomal or lysosomal compartments.

    • Meriem Belabed
    • , François-Xavier Mauvais
    •  & Gaël Ménasché

  • Article
    | Open Access

    Major Histocompatibility Complex (MHC) class I molecules present tightly binding peptides on the cell surface for recognition by cytotoxic T cells. Here, the authors present the crystal structures of a disulfide-stabilized human MHC class I molecule in the peptide-free state and bound with dipeptides, and find that peptide binding is accompanied by concerted conformational switches of the amino acid side chains in the binding pockets.

    • Raghavendra Anjanappa
    • , Maria Garcia-Alai
    •  & Rob Meijers

  • Article
    | Open Access

    The response to immunotherapy of melanoma patients is heterogeneous. Here, the authors demonstrate that a high expression of the two major components of the immunoproteasome, PSMB8 and PSMB9, modulates the production of HLA peptides and it is predictive of better survival and improved response to immune-checkpoint inhibitors of melanoma patients.

    • Shelly Kalaora
    • , Joo Sang Lee
    •  & Yardena Samuels

  • Article
    | Open Access

    Lymphatic endothelial cells (LECs) can cross-present antigen to naïve CD8+ T cells, but the significance of this interaction was unclear. Here the authors show that LECs directly induce CD8+ T cell differentiation with memory-like phenotypes, migration patterns and transcriptome, which can later be recalled to promote effector immunity and protection from Listeria infection.

    • Efthymia Vokali
    • , Shann S. Yu
    •  & Melody A. Swartz

  • Article
    | Open Access

    Langerhans cells (LC) can prime tolerogenic as well as immunogenic responses in the skin. Here the authors show, by transcriptomic, epigenetic and CRISPR editing analyses, that during LC migration and maturation the transcription factor IRF4 regulates expression of antigen presentation and co-stimulatory gene modules while attenuating inflammatory response genes.

    • Sofia Sirvent
    • , Andres F. Vallejo
    •  & Marta E. Polak

  • Article
    | Open Access

    Microfold cells (M cells) sit at the gut epithelial surface to sample antigens and maintain local immune homeostasis. Here the authors show that M cells are feedback-regulated by M cell-originated osteoprotegerin (OPG) to suppress RNAKL-induced M cell differentiation, and that OPG deficiency alters both gut colitis and infection phenotypes.

    • Shunsuke Kimura
    • , Yutaka Nakamura
    •  & Koji Hase

  • Article
    | Open Access

    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.

    • Catarina F. Almeida
    • , Srinivasan Sundararaj
    •  & Jamie Rossjohn

  • Article
    | Open Access

    High-throughput assays for TCR specificity are a bottleneck in understanding T cell immunity and harnessing it for medicine. Here the authors develop a functional screening method to identify T cell specificity in the natural context of peptide-MHC presentation, enabling detection of physiologically relevant T cell antigens from large libraries of peptide-coding sequences.

    • Govinda Sharma
    • , Craig M. Rive
    •  & Robert A. Holt

  • Article
    | Open Access

    Severe malaria can be associated with respiratory complications. Here, the authors show that malaria-associated pulmonary vascular damage is a consequence of IFNγ-activated lung endothelial cells capturing, processing, and cross-presenting malaria parasite antigen to specific CD8+ T cells induced during infection.

    • Carla Claser
    • , Samantha Yee Teng Nguee
    •  & Laurent Renia

  • Article
    | Open Access

    In multiple sclerosis (MS), antigen-presenting cells inducing cytotoxic T cell response against mature oligodendrocytes remain to be identified. Here the authors show that oligodendrocyte precursors cross-present antigen taken up from mature oligodendrocytes, and are targeted by cytotoxic T cells in cell culture and in an animal model of MS.

    • Leslie Kirby
    • , Jing Jin
    •  & Peter A. Calabresi

  • Article
    | Open Access

    Various host factors may impact within-host pathogen evolution. Here, the authors develop a Bayesian approach for identifying host-pathogen interactions using large data sets of pathogen diversity, and apply it to investigate HLA-induced selection in the HIV-1 genome.

    • Duncan S. Palmer
    • , Isaac Turner
    •  & Gil McVean

  • Article
    | Open Access

    CTL responses are critical in protection against pathogens. Here, using mass spectrometry and flow cytometry, the authors characterize the kinetics of influenza A virus class I MHC epitopes cross-presented in professional antigen presenting cells and identify new epitopes that elicit T cell responses in infected mice.

    • Ting Wu
    • , Jing Guan
    •  & Nicole L. La Gruta

  • Article
    | Open Access

    Gut lumen antigens must be continuously sampled by the immune system to maintain proper immune homeostasis. Here the authors show that activated CCR6+CCR1+GL7- gut B cells retrieve lumen antigens from specialized M cells and transfer them across the subepithelial dome in the Peyer’s patch to contribute to the maintenance of gut humoral immunity.

    • Rathan Joy Komban
    • , Anneli Strömberg
    •  & Nils Lycke

  • Article
    | Open Access

    Both thymic epithelial cells and dendritic cells present self antigens in the thymus to mediate thymic selection and T cell tolerance. Here the authors quantify, using two-photon live imaging of mouse thymic slices, the relative contribution of these two cell types, as well as the effects of antigen cross-presentation by dendritic cells, during tolerance induction.

    • J. N. Lancaster
    • , H. M. Thyagarajan
    •  & L. I. R. Ehrlich

  • Article
    | Open Access

    Here the authors examine how m6A modification is involved in innate immunity. They show that RNA methyltransferase Mettl3-mediated mRNA m6A methylation promotes dendritic cell (DC) activation and function, and in promoting DC-based T cells responses.

    • Huamin Wang
    • , Xiang Hu
    •  & Xuetao Cao

  • Article
    | Open Access

    For T cells, functional antigen receptors are selected in the thymus from a pre-selection repertoire by interaction with self MHCs. Here the authors show that specific, non-germline coded features located in the complementarity determining region 3 of the pre-selection antigen receptors are essential for the selection of MHC-restricted repertoire.

    • Jinghua Lu
    • , François Van Laethem
    •  & Peter D. Sun

  • Article
    | Open Access

    Anti-human leukocyte antigen (HLA) antibodies are important mediators of alloresponses, but structural insights on antibody:HLA interaction are still lacking. Here the authors provide a 2.4 Å structure of antibody:HLA complex, and also analyse HLA features important for other HLA-interacting molecules, to enhance our understanding of alloimmunity.

    • Yue Gu
    • , Yee Hwa Wong
    •  & Paul A. MacAry

  • Article
    | Open Access

    Signalling of the B cell receptor (BCR) is pivotal for survival and activation of naïve B cells. Here the authors show, using super-resolution microscopy techniques, that BCRs exist primarily as monomers and dimers in resting B cells, and oligomerize only on stimulation, thereby implicating a function of BCR clustering patterns on B cell biology.

    • Maria Angela Gomes de Castro
    • , Hanna Wildhagen
    •  & Felipe Opazo

  • Article
    | Open Access

    Microfold cells (M-cell) are specialized cells of the intestine that sample luminal microbiota and dietary antigens. Here the authors show that epithelial non-canonical NFκB signalling, as induced by NIK, is important for M-cells maintenance, yet constitutive NIK activation is associated with gut inflammation and inflammatory bowel disease.

    • Sadeesh K. Ramakrishnan
    • , Huabing Zhang
    •  & Yatrik M. Shah

  • Article
    | Open Access

    Antigen present and presented in the structures of the skin can result in immune responses that elicit tolerance, protective immunity or allergy, depending on the immunological context. Here the authors describe a key role for the hair follicle and CD11b+ dendritic cells in the priming of local antigenic tolerance.

    • Leticia Tordesillas
    • , Daniel Lozano-Ojalvo
    •  & M. Cecilia Berin

  • Article
    | Open Access

    Human leukocyte antigens (HLA) are multi-allelic and polymorphic genes that present antigens to immune cells for inducing protective immunity. Here, using systems biology and structural approaches, the authors show that micropolymorphism of three HLA has effects beyond the modulation of antigen diversity.

    • Patricia T. Illing
    • , Phillip Pymm
    •  & Anthony W. Purcell

  • Article
    | Open Access

    The CD1d pathway present lipid antigens resulting in the activation of iNKT cells but the complete pathway remains to be fully elucidated. Here, Chandra et al. use an siRNA screen and identify Mrp1 as crucial for CD1d lipid presentation and activation of iNKT in the context of Streptococcus pneumoniae infection.

    • Shilpi Chandra
    • , James Gray
    •  & Mitchell Kronenberg

  • Article
    | Open Access

    Langerhans cells (LC) and langerin-expressing conventional dendritic cells are made from distinct progenitors and enriched in the distinct microenvironments of the skin. Here the authors show that these immune cells are regulated by retinoic acid receptor alpha (RARα) via simultaneous induction of LC-promoting Runx3 and repression of LC-inhibiting C/EBPβ.

    • Seika Hashimoto-Hill
    • , Leon Friesen
    •  & Chang H. Kim

  • Article
    | Open Access

    RNA editing is a biological process that creates sequence variation. Here the authors show that peptides generated as a consequence of RNA editing are naturally presented by human leukocyte antigen (HLA) and serve as antigens to elicit anti-tumour immune responses.

    • Minying Zhang
    • , Jens Fritsche
    •  & Patrick Hwu

  • Article
    | Open Access

    Acquired resistance is a major problem in cancer immunotherapy. Here the authors report a study of two patients with Merkel cell carcinoma under immunotherapy treatment who develop resistance after deep responses for >1 year and identified a novel mechanism of acquired, gene-specific transcriptional suppression of HLAs.

    • K. G. Paulson
    • , V. Voillet
    •  & A. G. Chapuis

  • Article
    | Open Access

    Plasmacytoid dendritic cells (pDC) are an important regulator of immune responses. Here the authors show that pDC precursors, similar to peripheral blood-derived pDCs, can be differentiated from human CD34+ hematopoietic stem and progenitor cells, with type I/II IFN priming being required for their functional maturation and differentiation.

    • A. Laustsen
    • , R. O. Bak
    •  & M. R. Jakobsen

  • Article
    | Open Access

    Donor-derived dendritic cells (do-DC) in the graft can contribute to the induction of alloimmunity and tissue rejection, but how do-DC can be targeted for improving graft survival is unclear. Here the authors show that reducing MHC-II expression on do-DCs by DnaK pre-treatment can decrease the priming of alloimmunity and prolong graft survival in mouse models.

    • Thiago J. Borges
    • , Naoka Murakami
    •  & Cristina Bonorino

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