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Frontiers in Immunology 2022The lungs are constantly exposed to environmental and infectious agents such as dust, viruses, fungi, and bacteria that invade the lungs upon breathing. The lungs are... (Review)
Review
The lungs are constantly exposed to environmental and infectious agents such as dust, viruses, fungi, and bacteria that invade the lungs upon breathing. The lungs are equipped with an immune defense mechanism that involves a wide variety of immunological cells to eliminate these agents. Various types of dendritic cells (DCs) and macrophages (MACs) function as professional antigen-presenting cells (APCs) that engulf pathogens through endocytosis or phagocytosis and degrade proteins derived from them into peptide fragments. During this process, DCs and MACs present the peptides on their major histocompatibility complex class I (MHC-I) or MHC-II protein complex to naïve CD8 or CD4 T cells, respectively. In addition to these cells, recent evidence supports that antigen-specific effector and memory T cells are activated by other lung cells such as endothelial cells, epithelial cells, and monocytes through antigen presentation. In this review, we summarize the molecular mechanisms of antigen presentation by APCs in the lungs and their contribution to immune response.
Topics: Antigen Presentation; Cells, Cultured; Dendritic Cells; Endothelial Cells; Lung
PubMed: 35615351
DOI: 10.3389/fimmu.2022.860915 -
Current Opinion in Immunology Jun 2017
Topics: Antigen Presentation; Antigens; Humans; T-Lymphocytes
PubMed: 28716443
DOI: 10.1016/j.coi.2017.07.002 -
Clinical Immunology (Orlando, Fla.) Mar 2017Autophagy is a highly conserved protein degradation pathway from yeasts to humans that is essential for removing protein aggregates and misfolded proteins in healthy... (Review)
Review
Autophagy is a highly conserved protein degradation pathway from yeasts to humans that is essential for removing protein aggregates and misfolded proteins in healthy cells. Recently, autophagy-related genes polymorphisms have been implicated in several autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, psoriasis, and multiple sclerosis. Numerous studies reveal autophagy and autophagy-related proteins also participate in immune regulation. Conditional deletions of autophagy-related proteins in mice have rendered protection from experimental autoimmune encephalomyelitis, and TNF-mediated joint destruction in animal models of multiple sclerosis and experimental arthritis respectively. As autophagy is strongly implicated in immune functions such as removal of intracellular bacteria, inflammatory cytokine secretion, antigen presentation, and lymphocyte development, in this review we summarized current understanding of the roles of autophagy and autophagy proteins in autoimmune diseases.
Topics: Animals; Antigen Presentation; Autoimmune Diseases; Autoimmunity; Autophagy; Humans
PubMed: 28095319
DOI: 10.1016/j.clim.2017.01.007 -
Frontiers in Immunology 2022
Topics: Antigen Presentation; Antigen-Presenting Cells; Histocompatibility Antigens Class II; Humans; Immune System Diseases
PubMed: 36159790
DOI: 10.3389/fimmu.2022.993393 -
Immunogenetics Mar 2019Immune response to disease requires coordinated expression of an army of molecules. The highly polymorphic MHC class I and class II molecules are key to control of... (Review)
Review
Immune response to disease requires coordinated expression of an army of molecules. The highly polymorphic MHC class I and class II molecules are key to control of specificity of antigen presentation. Processing of the antigen, to peptides or other moieties, requires other sets of molecules. For classical class I, this includes TAP peptide transporters, proteasome components and Tapasin, genes which are encoded within the MHC. Similarly, HLA-DO and -DM, which influence presentation by HLA class II molecules, are encoded in the MHC region. Analysis of MHC mutants, including point mutations and large deletions, has been central to understanding the roles of these genes. Mouse genetics has also played a major role. Many other genes have been identified including those controlling expression of HLA class I and class II at the transcriptional level. Another genetic approach that has provided insight has been the analysis of microorganisms, including viruses and bacteria that escape immune recognition by blocking these antigen processing and presentation pathways. Here, we provide a brief history of the genetic approaches, both traditional and modern, that have been used in the quest to understand antigen processing and presentation.
Topics: Animals; Antigen Presentation; Humans; Immunogenetics; Major Histocompatibility Complex
PubMed: 30215098
DOI: 10.1007/s00251-018-1082-2 -
Journal For Immunotherapy of Cancer Aug 2020Knowledge about and identification of T cell tumor antigens may inform the development of T cell receptor-engineered adoptive cell transfer or personalized cancer... (Review)
Review
BACKGROUND
Knowledge about and identification of T cell tumor antigens may inform the development of T cell receptor-engineered adoptive cell transfer or personalized cancer vaccine immunotherapy. Here, we review antigen processing and presentation and discuss limitations in tumor antigen prediction approaches.
METHODS
Original articles covering antigen processing and presentation, epitope discovery, and in silico T cell epitope prediction were reviewed.
RESULTS
Natural processing and presentation of antigens is a complex process that involves proteasomal proteolysis of parental proteins, transportation of digested peptides into the endoplasmic reticulum, loading of peptides onto major histocompatibility complex (MHC) class I molecules, and shuttling of peptide:MHC complexes to the cell surface. A number of T cell tumor antigens have been experimentally validated in patients with cancer. Assessment of predicted MHC class I binding and total score for these validated T cell antigens demonstrated a wide range of values, with nearly one-third of validated antigens carrying an IC of greater than 500 nM.
CONCLUSIONS
Antigen processing and presentation is a complex, multistep process. In silico epitope prediction techniques can be a useful tool, but comprehensive experimental testing and validation on a patient-by-patient basis may be required to reliably identify T cell tumor antigens.
Topics: Antigen Presentation; Female; Humans; Immunotherapy; Male; Neoplasms
PubMed: 32859742
DOI: 10.1136/jitc-2020-001111 -
Journal of Controlled Release :... Oct 2017Although vaccination is historically one of the most successful strategies for the prevention of infectious diseases, development of vaccines for cancer and many chronic... (Review)
Review
Although vaccination is historically one of the most successful strategies for the prevention of infectious diseases, development of vaccines for cancer and many chronic infections, such as HIV, malaria, and tuberculosis, has remained a challenge. Strong and long-lasting antigen-specific T cell responses are critical for therapy of these diseases. A major challenge in achieving a robust CD8+ T cell response is the requirement of spatio-temporal orchestration of antigen cross-presentation in antigen-presenting cells with innate stimulation. Here, we discuss the development of nanoparticle vaccine (nanovaccine) that modulates the innate immune system and enhances adaptive immunity with reduced toxicity. We address how nanovaccines can integrate multiple functions, such as lymph node targeting, antigen presentation, and stimulation of innate immunity, to achieve a robust T cell response for immunotherapy.
Topics: Animals; Antigen Presentation; Cancer Vaccines; Humans; Immunotherapy; Nanoparticles
PubMed: 28336379
DOI: 10.1016/j.jconrel.2017.03.033 -
Journal of Translational Medicine Jan 2024Cancer-associated fibroblasts (CAFs) are heterogeneous and can influence the progression of prostate cancer in multiple ways; however, their capacity to present and...
BACKGROUND
Cancer-associated fibroblasts (CAFs) are heterogeneous and can influence the progression of prostate cancer in multiple ways; however, their capacity to present and process antigens in PRAD has not been investigated. In this study, antigen presentation and process-related CAFs (APPCAFs) were identified using bioinformatics, and the clinical implications of APPCAF-related signatures in PRAD were investigated.
METHODS
SMART technology was used to sequence the transcriptome of primary CAFs isolated from patients undergoing different treatments. Differential expression gene (DEG) screening was conducted. A CD4 + T-cell early activation assay was used to assess the activation degree of CD4 + T cells. The datasets of PRAD were obtained from The Cancer Genome Atlas (TCGA) database and NCBI Gene Expression Omnibus (GEO), and the list of 431 antigen presentation and process-related genes was obtained from the InnateDB database. Subsequently, APP-related CAFs were identified by nonnegative matrix factorization (NMF) based on a single-cell seq (scRNA) matrix. GSVA functional enrichment analyses were performed to depict the biological functions. A risk signature based on APPCAF-related genes (APPCAFRS) was developed by least absolute shrinkage and selection operator (LASSO) regression analysis, and the independence of the risk score as a prognostic factor was evaluated by univariate and multivariate Cox regression analyses. Furthermore, a biochemical recurrence-free survival (BCRFS)-related nomogram was established, and immune-related characteristics were assessed using the ssGSEA function. The immune treatment response in PRAD was further analyzed by the Tumor Immune Dysfunction and Exclusion (TIDE) tool. The expression levels of hub genes in APPCAFRS were verified in cell models.
RESULTS
There were 134 upregulated and 147 downregulated genes, totaling 281 differentially expressed genes among the primary CAFs. The functions and pathways of 147 downregulated DEGs were significantly enriched in antigen processing and presentation processes, MHC class II protein complex and transport vesicle, MHC class II protein complex binding, and intestinal immune network for IgA production. Androgen withdrawal diminished the activation effect of CAFs on T cells. NMF clustering of CAFs was performed by APPRGs, and pseudotime analysis yielded the antigen presentation and process-related CAF subtype CTSK + MRC2 + CAF-C1. CTSK + MRC2 + CAF-C1 cells exhibited ligand‒receptor connections with epithelial cells and T cells. Additionally, we found a strong association between CTSK + MRC2 + CAF-C1 cells and inflammatory CAFs. Through differential gene expression analysis of the CTSK + MRC2 + CAF-C1 and NoneAPP-CAF-C2 subgroups, 55 significant DEGs were identified, namely, APPCAFRGs. Based on the expression profiles of APPCAFRGs, we divided the TCGA-PRAD cohort into two clusters using NMF consistent cluster analysis, with the genetic coefficient serving as the evaluation index. Four APPCAFRGs, THBS2, DPT, COL5A1, and MARCKS, were used to develop a prognostic signature capable of predicting BCR occurrence in PRAD patients. Subsequently, a nomogram with stability and accuracy in predicting BCR was constructed based on Gleason grade (p = n.s.), PSA (p < 0.001), T stage (p < 0.05), and risk score (p < 0.01). The analysis of immune infiltration showed a positive correlation between the abundance of resting memory CD4 + T cells, M1 macrophages, resting dendritic cells, and the risk score. In addition, the mRNA expression levels of THBS2, DPT, COL5A1, and MARCKS in the cell models were consistent with the results of the bioinformatics analysis.
CONCLUSIONS
APPCAFRS based on four potential APPCAFRGs was developed, and their interaction with the immune microenvironment may play a crucial role in the progression to castration resistance of PRAD. This novel approach provides valuable insights into the pathogenesis of PRAD and offers unexplored targets for future research.
Topics: Male; Humans; Antigen Presentation; Cancer-Associated Fibroblasts; Prostatic Neoplasms; Sequence Analysis, RNA; Algorithms; Prognosis; Tumor Microenvironment
PubMed: 38221616
DOI: 10.1186/s12967-023-04807-y -
Frontiers in Immunology 2022
Topics: Humans; Antigen Presentation; Autoimmunity; Aminopeptidases; Immune System Diseases
PubMed: 36311705
DOI: 10.3389/fimmu.2022.1055152 -
Neurotherapeutics : the Journal of the... Oct 2016Stroke induces a local inflammatory reaction and a plethora of innate immune responses in the brain where antigen-presenting cells become prominent. However, to date, it... (Review)
Review
Stroke induces a local inflammatory reaction and a plethora of innate immune responses in the brain where antigen-presenting cells become prominent. However, to date, it is still unclear whether antigen presentation is relevant to the neuropathological and functional outcome of stroke. Stroke does not trigger overt autoimmune reactions, but neural antigens have been found in lymphoid tissues of patient with stroke and it is unknown whether they promote tolerance or immune reactions that under certain conditions might contribute to the functional worsening observed in some patients. Autoantibodies to neural molecules have also been reported in patients with stroke, but the subclass of antibodies is important for their function, and the contribution of such findings to stroke outcome is not yet clear. Notably, stroke induces immunodepression highlighted by a transient lymphopenia, lymphoid organ atrophy, and monocyte deactivation. While these effects might reduce the chances of autoreactivity, they increase the risk of infection in patients with stroke and most frequently in those with severe stroke. Therefore any potential brain protective effect of stroke-induced immunodepression by attenuating or preventing lymphocyte-mediated brain damage is confounded by stroke severity and an increased incidence of infections. Systemic inflammation due to a number of comorbidities that are frequent in patients with stroke is also associated to a poor outcome. Herein, we review some relevant findings regarding the identification of neural antigens in stroke and discuss their potential contribution to the functional outcome of stroke.
Topics: Animals; Antigen Presentation; Humans; Immune System; Stroke
PubMed: 27514673
DOI: 10.1007/s13311-016-0469-8