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Molecular Immunology Feb 2021The high expression of CD1a on Langerhans cells in normal human skin suggests a central role for this lipid antigen presenting molecule in skin homeostasis and immunity.... (Review)
Review
The high expression of CD1a on Langerhans cells in normal human skin suggests a central role for this lipid antigen presenting molecule in skin homeostasis and immunity. Although the lipid antigen presenting function of CD1a has been known for years, the physiological and pathological functions of the CD1a system in human skin remain incompletely understood. This review provides an overview of this active area of investigation, and discusses recent insights into the functions of CD1a, CD1a-restricted T cells, and lipid antigens in inflammatory and allergic skin disease. We include recent publications and work presented at the biennial CD1-MR1 EMBO workshop held in 2019 in Oxford, regarding lipids that increase and those that decrease T cell responses to CD1a.
Topics: Antigen Presentation; Antigens, CD1; Humans; Langerhans Cells; Lymphocyte Activation; Skin; Skin Diseases; T-Lymphocytes
PubMed: 33348245
DOI: 10.1016/j.molimm.2020.12.006 -
Annals of Oncology : Official Journal... Dec 2017Dendritic cells (DCs) are the main professional antigen-presenting cells for induction of T-cell adaptive responses. Cancer cells express tumor antigens, including...
Dendritic cells (DCs) are the main professional antigen-presenting cells for induction of T-cell adaptive responses. Cancer cells express tumor antigens, including neoantigens generated by nonsynonymous mutations, but are poor for antigen presentation and for providing costimulatory signals for T-cell priming. Mounting evidence suggests that antigen transfer to DCs and their surrogate presentation on major histocompatibility complex class I and II molecules together with costimulatory signals is paramount for induction of viral and cancer immunity. Of the great diversity of DCs, BATF3/IRF8-dependent conventional DCs type 1 (cDC1) excel at cross-presentation of tumor cell-associated antigens. Location of cDC1s in the tumor correlates with improved infiltration by CD8+ T cells and tumor-specific T-cell immunity. Indeed, cDC1s are crucial for antitumor efficacy using checkpoint inhibitors and anti-CD137 agonist monoclonal antibodies in mouse models. Enhancement and exploitation of T-cell cross-priming by cDC1s offer opportunities for improved cancer immunotherapy, including in vivo targeting of tumor antigens to internalizing receptors on cDC1s and strategies to increase their numbers, activation and priming capacity within tumors and tumor-draining lymph nodes.
Topics: Animals; Antigen Presentation; Antigens, Neoplasm; Cross-Priming; Dendritic Cells; Humans; Neoplasms; T-Lymphocytes
PubMed: 28945841
DOI: 10.1093/annonc/mdx237 -
Biochemical Society Transactions Dec 2023Advances in immunotherapy in the last decade have revolutionized treatment paradigms across multiple cancer diagnoses. However, only a minority of patients derive... (Review)
Review
Advances in immunotherapy in the last decade have revolutionized treatment paradigms across multiple cancer diagnoses. However, only a minority of patients derive durable benefit and progress with traditional approaches, such as cancer vaccines, remains unsatisfactory. A key to overcoming these barriers resides with a deeper understanding of tumor antigen presentation and the complex and dynamic heterogeneity of tumor-infiltrating antigen-presenting cells (APCs). Reminiscent of the 'second touch' hypothesis proposed by Klaus Ley for CD4+ T cell differentiation, the acquisition of full effector potential by lymph node- primed CD8+ T cells requires a second round of co-stimulation at the site where the antigen originated, i.e. the tumor bed. The tumor stroma holds a prime role in this process by hosting specialized APC niches, apparently distinct from tertiary lymphoid structures, that support second antigenic touch encounters and CD8+ T cell effector proliferation and differentiation. We propose that APC within second-touch niches become licensed for co-stimulation through stromal-derived instructive signals emulating embryonic or wound-healing provisional matrix remodeling. These immunostimulatory roles of stroma contrast with its widely accepted view as a physical and functional 'immune barrier'. Stromal control of antigen presentation makes evolutionary sense as the host stroma-tumor interface constitutes the prime line of homeostatic 'defense' against the emerging tumor. In this review, we outline how stroma-derived signals and cells regulate tumor antigen presentation and T-cell effector differentiation in the tumor bed. The re-definition of tumor stroma as immune rheostat rather than as inflexible immune barrier harbors significant untapped therapeutic opportunity.
Topics: Humans; Antigen Presentation; Antigen-Presenting Cells; Neoplasms; CD4-Positive T-Lymphocytes; Lymphocyte Activation; Antigens, Neoplasm; CD8-Positive T-Lymphocytes; Dendritic Cells
PubMed: 38031753
DOI: 10.1042/BST20221083 -
Molecular Immunology Sep 2018B cell encounter with antigen displayed on antigen-presenting cells leads to B cell immune synapse formation, internalisation of the antigen, and stimulation of antibody... (Review)
Review
B cell encounter with antigen displayed on antigen-presenting cells leads to B cell immune synapse formation, internalisation of the antigen, and stimulation of antibody responses. The sensitivity with which B cells detect antigen, and the quality and quantity of antigen that B cells acquire, depend upon mechanical properties of the immune synapse including interfacial tension, the strength of intermolecular bonds, and the compliance of the molecules and membranes that participate in antigen presentation. In this review, we discuss our current understanding of how these various physical parameters influence B cell antigen extraction in the immune synapse and how a more comprehensive understanding of B cell mechanics may promote the development of new approaches to stimulate the production of desired antibodies.
Topics: Animals; Antigen Presentation; Antigen-Presenting Cells; Antigens; B-Lymphocytes; Biophysical Phenomena; Humans; Immunological Synapses
PubMed: 30036798
DOI: 10.1016/j.molimm.2018.07.018 -
Einstein (Sao Paulo, Brazil) 2015The setting for the occurrence of an immune response is that of the need to cope with a vast array of different antigens from both pathogenic and non-pathogenic sources.... (Review)
Review
The setting for the occurrence of an immune response is that of the need to cope with a vast array of different antigens from both pathogenic and non-pathogenic sources. When the first barriers against infection and innate defense fail, adaptive immune response enters the stage for recognition of the antigens by means of extremely variable molecules, namely immunoglobulins and T-cell receptors. The latter recognize the antigen exposed on cell surfaces, in the form of peptides presented by the HLA molecule. The first part of this review details the central role played by these molecules, establishing the close connection existing between their structure and their antigen presenting function.
Topics: Alleles; Antigen Presentation; HLA Antigens; Humans; Major Histocompatibility Complex
PubMed: 25807245
DOI: 10.1590/S1679-45082015RB3122 -
Cellular & Molecular Immunology May 2016The liver is an organ in which antigen-specific T-cell responses manifest a bias toward immune tolerance. This is clearly seen in the rejection of allogeneic liver... (Review)
Review
The liver is an organ in which antigen-specific T-cell responses manifest a bias toward immune tolerance. This is clearly seen in the rejection of allogeneic liver transplants, and multiple other phenomena suggest that this effect is more general. These include tolerance toward antigens introduced via the portal vein, immune failure to several hepatotropic viruses, the lack of natural liver-stage immunity to malaria parasites, and the frequent metastasis of cancers to the liver. Here we review the mechanisms by which T cells engage with hepatocellular antigens, the context in which such encounters occur, and the mechanisms that act to suppress a full T-cell response. While many mechanisms play a role, we will argue that two important processes are the constraints on the cross-presentation of hepatocellular antigens, and the induction of negative feedback inhibition driven by interferons. The constant exposure of the liver to microbial products from the intestine may drive innate immunity, rendering the local environment unfavorable for specific T-cell responses through this mechanism. Nevertheless, tolerance toward hepatocellular antigens is not monolithic and under specific circumstances allows both effective immunity and immunopathology.
Topics: Animals; Antigen Presentation; Antigen-Presenting Cells; Hepatocytes; Humans; Immune Tolerance; Inflammation; Signal Transduction
PubMed: 26924525
DOI: 10.1038/cmi.2015.109 -
Biomedicine & Pharmacotherapy =... Dec 2023Cross-presentation (XPT) is an adaptation of the cellular process in which dendritic cells (DCs) present exogenous antigens on major histocompatibility complex (MHC)... (Review)
Review
Cross-presentation (XPT) is an adaptation of the cellular process in which dendritic cells (DCs) present exogenous antigens on major histocompatibility complex (MHC) class I molecules for recognition of the cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, resulting in immunity or tolerance. Recent advances in DCs have broadened our understanding of the underlying mechanisms of XPT and strengthened their application in tumor immunotherapy. In this review, we summarized the known mechanisms of XPT, including the receptor-mediated internalization of exogenous antigens, endosome escape, engagement of the other XPT-related proteins, and adjuvants, which significantly enhance the XPT capacity of DCs. Consequently, various strategies to enhance XPT can be adopted and optimized to improve outcomes of DC-based therapy.
Topics: Cross-Priming; Dendritic Cells; Antigen Presentation; Antigens; Histocompatibility Antigens Class I
PubMed: 37866002
DOI: 10.1016/j.biopha.2023.115758 -
Viruses Jan 2022Cytomegaloviruses (CMVs) are host species-specific and have adapted to their respective mammalian hosts during co-evolution. Host-adaptation is reflected by "private... (Review)
Review
Cytomegaloviruses (CMVs) are host species-specific and have adapted to their respective mammalian hosts during co-evolution. Host-adaptation is reflected by "private genes" that have specialized in mediating virus-host interplay and have no sequence homologs in other CMV species, although biological convergence has led to analogous protein functions. They are mostly organized in gene families evolved by gene duplications and subsequent mutations. The host immune response to infection, both the innate and the adaptive immune response, is a driver of viral evolution, resulting in the acquisition of viral immune evasion proteins encoded by private gene families. As the analysis of the medically relevant human cytomegalovirus by clinical investigation in the infected human host cannot make use of designed virus and host mutagenesis, the mouse model based on murine cytomegalovirus (mCMV) has become a versatile animal model to study basic principles of in vivo virus-host interplay. Focusing on the immune evasion of the adaptive immune response by CD8 T cells, we review here what is known about proteins of two private gene families of mCMV, the and the families, specifically the role of , , and in viral antigen presentation during acute and latent infection.
Topics: Animals; Antigen Presentation; Antigens, Viral; CD8-Positive T-Lymphocytes; Cytomegalovirus Infections; Disease Models, Animal; Host-Pathogen Interactions; Immune Evasion; Killer Cells, Natural; Mice; Mice, Inbred C57BL; Muromegalovirus; Viral Proteins
PubMed: 35062332
DOI: 10.3390/v14010128 -
The International Journal of... Dec 2022The lung is frequently and repeatedly exposed to invading pathogens and thus requires constant immunosurveillance. Professional antigen presenting cells (APCs),... (Review)
Review
The lung is frequently and repeatedly exposed to invading pathogens and thus requires constant immunosurveillance. Professional antigen presenting cells (APCs), including dendritic cells, engulf invading pathogens and present their peptides via major histocompatibility complexes (MHC) I and II, to CD8 or CD4 T cells. Epithelial cells and stromal cells (including fibroblasts) provide more than structural support, they are increasingly recognised as key players in the immune response, acting as non-professional APCs through interactions with antigen experienced T cells that migrate to the lung. The importance of the contributions of non-professional and professional APCs to T cell function in vivo, is currently unclear. This review summarises the roles of professional and non-professional APCs in lung immunity, at the steady state and following viral insult, with particular emphasis on their ability to interact with and influence T cells.
Topics: Humans; Antigen Presentation; Antigen-Presenting Cells; CD4-Positive T-Lymphocytes; Lung; Major Histocompatibility Complex
PubMed: 36368596
DOI: 10.1016/j.biocel.2022.106331 -
Immunogenetics Mar 2019Presentation of peptide antigens by MHC-II proteins is prerequisite to effective CD4 T cell tolerance to self and to recognition of foreign antigens. Antigen uptake and... (Review)
Review
Presentation of peptide antigens by MHC-II proteins is prerequisite to effective CD4 T cell tolerance to self and to recognition of foreign antigens. Antigen uptake and processing pathways as well as expression of the peptide exchange factors HLA-DM and HLA-DO differ among the various professional and non-professional antigen-presenting cells and are modulated by cell developmental state and activation. Recent studies have highlighted the importance of these cell-specific factors in controlling the source and breadth of peptides presented by MHC-II under different conditions. During inflammation, increased presentation of selected self-peptides has implications for maintenance of peripheral tolerance and autoimmunity.
Topics: Animals; Antigen Presentation; Antigen-Presenting Cells; Histocompatibility Antigens Class II; Humans; Immune Tolerance; Inflammation; T-Lymphocytes
PubMed: 30421030
DOI: 10.1007/s00251-018-1095-x