Spotlight on TAP and its vital role in antigen presentation and cross-presentation

2022 ◽  
Vol 142 ◽  
pp. 105-119
Author(s):  
Ian Mantel ◽  
Barzan A. Sadiq ◽  
J. Magarian Blander
Keyword(s):  
Antigen Presentation ◽  
Vital Role ◽  
Cross Presentation

scholarly journals Predominant Role for Directly Transfected Dendritic Cells in Antigen Presentation to CD8+ T Cells after Gene Gun Immunization

1998 ◽  
Vol 188 (6) ◽  
pp. 1075-1082 ◽  
Author(s):  
Angel Porgador ◽  
Kari R. Irvine ◽  
Akiko Iwasaki ◽  
Brian H. Barber ◽  
Nicholas P. Restifo ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Antigen Presentation ◽  
Cd8 T Cells ◽  
Cytotoxic T Cell ◽  
Gene Gun ◽  
Cross Presentation

Cutaneous gene (DNA) bombardment results in substantial expression of the encoded antigen in the epidermal layer as well as detectable expression in dendritic cells (DC) in draining lymph nodes (LNs). Under these conditions, two possible modes of DC antigen presentation to naive CD8+ T cells might exist: (a) presentation directly by gene-transfected DC trafficking to local lymph nodes, and (b) cross-presentation by untransfected DC of antigen released from or associated with transfected epidermal cells. The relative contributions of these distinct modes of antigen presentation to priming for cytotoxic T cell (CTL) responses have not been clearly established. Here we show that LN cells directly expressing the DNA-encoded antigen are rare; 24 h after five abdominal skin bombardments, the number of these cells does not exceed 50–100 cells in an individual draining LN. However, over this same time period, the total number of CD11c+ DC increases more than twofold, by an average of 20,000–30,000 DC per major draining node. This augmentation is due to gold bombardment and is independent of the presence of plasmid DNA. Most antigen-bearing cells in the LNs draining the site of DNA delivery appear to be DC and can be depleted by antibodies to an intact surface protein encoded by cotransfected DNA. This finding of predominant antigen presentation by directly transfected cells is also consistent with data from studies on cotransfection with antigen and CD86-encoding DNA, showing that priming of anti-mutant influenza nucleoprotein CTLs with a single immunization is dependent upon coexpression of the DNAs encoding nucleoprotein and B7.2 in the same cells. These observations provide insight into the relative roles of direct gene expression and cross-presentation in CD8+ T cell priming using gene gun immunization, and indicate that augmentation of direct DC gene expression may enhance such priming.

scholarly journals The ABCs of Antigen Presentation by Stromal Non-Professional Antigen-Presenting Cells

2021 ◽  
Vol 23 (1) ◽  
pp. 137
Author(s):  
Tom J. Harryvan ◽  
Sabine de Lange ◽  
Lukas J. A. C. Hawinkels ◽  
Els M. E. Verdegaal
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Cell Function ◽  
Antigen Presenting Cells ◽  
Cell Types ◽  
T Cell Response ◽  
Cross Presentation ◽  
Antigen Presenting

Professional antigen-presenting cells (APCs), such as dendritic cells and macrophages, are known for their ability to present exogenous antigens to T cells. However, many other cell types, including endothelial cells, fibroblasts, and lymph node stromal cells, are also capable of presenting exogenous antigens to either CD8+ or CD4+ T cells via cross-presentation or major histocompatibility complex (MHC) class II-mediated presentation, respectively. Antigen presentation by these stromal nonprofessional APCs differentially affect T cell function, depending on the type of cells that present the antigen, as well as the local (inflammatory) micro-environment. It has been recently appreciated that nonprofessional APCs can, as such, orchestrate immunity against pathogens, tumor survival, or rejection, and aid in the progression of various auto-immune pathologies. Therefore, the interest for these nonprofessional APCs is growing as they might be an important target for enhancing various immunotherapies. In this review, the different nonprofessional APCs are discussed, as well as their functional consequences on the T cell response, with a focus on immuno-oncology.

scholarly journals Genomic programming of antigen cross-presentation in IRF4-expressing human Langerhans cells

2019 ◽  
Author(s):  
Marta E Polak ◽  
Sofia Sirvent ◽  
Kalum Clayton ◽  
James Davies ◽  
Andres F. Vallejo ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Transcription Factor ◽  
Antigen Presentation ◽  
Langerhans Cells ◽  
Mhc I ◽  
Cross Presentation ◽  
Mhc Ii ◽  
T Cell Immune Responses ◽  
Dependent Protein ◽  
Chromatin Profiling

AbstractLangerhans cells (LCs) in the epidermis present MHC I and MHC II-restricted antigens thereby priming either CD8 or CD4 T cell immune responses. The genomic programs and transcription factors regulating antigen presentation in LCs remain to be elucidated. We show human LCs are highly efficient in MHC I-antigen cross-presentation but lack the transcription factor IRF8 that is critical in dendritic cells. LC migration from the epidermis enhances their ability to cross-present antigens and is accompanied by the induction of the transcription factor IRF4, whose expression is correlated by scRNA-seq with genes involved in ubiquitin-dependent protein degradation. Chromatin profiling reveals enrichment of EICE and AICE composite DNA binding motifs in regulatory regions of antigen-presentation genes, which can be recognized by IRF4 in conjunction with PU.1 or BATF3 expressed in LCs. Thus, the genomic programming of human LCs including inducible expression of IRF4 with enhanced cross-presentation distinguishes them from conventional dendritic cells.

scholarly journals Platelet EVs contain an active proteasome involved in protein processing for antigen presentation via MHC-I molecules

Blood ◽  
2021 ◽  
Author(s):  
Genevieve Marcoux ◽  
Audrée Laroche ◽  
Stephan Hasse ◽  
Marie Bellio ◽  
Maroua Mbarik ◽  
...  
Keyword(s):  
Antigen Presentation ◽  
Protein Processing ◽  
Functional Protein ◽  
Mhc I ◽  
Cross Presentation ◽  
System A ◽  
Activated Platelets ◽  
T Lymphocyte Proliferation ◽  
Cd8 T Lymphocyte ◽  
Spleen And Lymph Nodes

In addition to their hemostatic role, platelets play a significant role in immunity. Once activated, platelets release extracellular vesicles (EVs) formed by budding of their cytoplasmic membranes. Because of their heterogeneity, platelet EVs (PEVs) are thought to perform diverse functions. It is unknown, however, whether the proteasome is transferred from platelets to PEVs or whether its function is retained. We hypothesized that functional protein processing and antigen presentation machinery is transferred to PEVs by activated platelets. Using molecular and functional assays, we show that the active 20S proteasome is enriched in PEVs along with MHC-I and lymphocyte costimulatory molecules (CD40L and OX40L). Proteasome-containing PEVs were identified in healthy donor blood, but did not increase in platelet concentrates that caused adverse transfusion reactions. They were, however, augmented after immune complex injections in mice. The complete biodistribution of murine PEVs following injection into mice revealed that they could principally reach lymphoid organs such as spleen and lymph nodes, in addition to the bone marrow, and to a lesser extent liver and lungs. The PEV proteasome processed exogenous ovalbumin (OVA) and loaded its antigenic peptide onto MHC-I molecules which promoted OVA-specific CD8+ T lymphocyte proliferation. These results suggest that PEVs contribute to adaptive immunity through cross-presentation of antigens and have privileged access to immune cells through the lymphatic system, a tissue location that is inaccessible to platelets.

scholarly journals Central Tolerance to Tissue-specific Antigens Mediated by Direct and Indirect Antigen Presentation

2004 ◽  
Vol 200 (8) ◽  
pp. 1039-1049 ◽  
Author(s):  
Alena M. Gallegos ◽  
Michael J. Bevan
Keyword(s):  
T Cells ◽  
Antigen Presentation ◽  
Cd8 T Cells ◽  
Thymic Epithelial Cells ◽  
Clonal Deletion ◽  
Autoreactive T Cells ◽  
Tissue Specific ◽  
Central Tolerance ◽  
Cross Presentation ◽  
Specific Antigens

Intrathymic expression of tissue-specific antigens (TSAs) by medullary thymic epithelial cells (Mtecs) leads to deletion of autoreactive T cells. However, because Mtecs are known to be poor antigen-presenting cells (APCs) for tolerance to ubiquitous antigens, and very few Mtecs express a given TSA, it was unclear if central tolerance to TSA was induced directly by Mtec antigen presentation or indirectly by thymic bone marrow (BM)-derived cells via cross-presentation. We show that professional BM-derived APCs acquire TSAs from Mtecs and delete autoreactive CD8 and CD4 T cells. Although direct antigen presentation by Mtecs did not delete the CD4 T cell population tested in this study, Mtec presentation efficiently deleted both monoclonal and polyclonal populations of CD8 T cells. For developing CD8 T cells, deletion by BM-derived APC and by Mtec presentation occurred abruptly at the transitional, CD4high CD8low TCRintermediate stage, presumably as the cells transit from the cortex to the medulla. These studies reveal a cooperative relationship between Mtecs and BM-derived cells in thymic elimination of autoreactive T cells. Although Mtecs synthesize TSAs and delete a subset of autoreactive T cells, BM-derived cells extend the range of clonal deletion by cross-presenting antigen captured from Mtecs.

scholarly journals MHC class I antigen cross-presentation mediated by PapMV nanoparticles in human antigen-presenting cells is dependent on autophagy

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261987
Author(s):  
David Possamaï ◽  
Laïla-Aïcha Hanafi ◽  
Angélique Bellemare-Pelletier ◽  
Katia Hamelin ◽  
Paméla Thébault ◽  
...  
Keyword(s):  
Antigen Presentation ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Antigen Presenting Cells ◽  
Class I ◽  
Class I Mhc ◽  
Mhc I ◽  
Cross Presentation ◽  
Antigen Presenting ◽  
Papmv Nanoparticles

Nanoparticles made of the coat protein of papaya mosaic virus (PapMV) and a single-strand RNA were previously shown to be an efficient antigen presentation system for the trigger of cellular immunity. Engineering of PapMV nano with a cytotoxic T lymphocyte epitope was previously shown activating specific T lymphocytes through a proteasome-independent major histocompatibility complex class I (MHC-I) cross-presentation. In this study, we provide new insights into the mechanism of the MHC-I cross-presentation mediated by PapMV nanoparticles. We demonstrate that PapMV nanoparticles do not require the transporter associated with antigen presentation (TAP), but rather depend on lysosome acidification and cathepsin S protease activity for presentation of the T cell epitope. We have also linked the induction of autophagy with this vacuolar MHC-I cross-presentation process. Interestingly, autophagy is induced in antigen-presenting cells after PapMV nanoparticles exposure and inhibition of autophagy reduce MHC-I cross-presentation. This study demonstrates that autophagy is associated with TAP- and proteasome-independent MHC-I cross-presentation. A deeper understanding of the autophagy-dependent MHC-I cross-presentation will be useful in designing vaccination platforms that aim to trigger an efficient cytotoxic T lymphocyte response.

scholarly journals Intrahepatic Cross-Presentation and Hepatocellular Antigen Presentation Play Distinct Roles in the Induction of Hepatitis B Virus-Specific CD8+T Cell Responses

2018 ◽  
Vol 92 (21) ◽  
Author(s):  
Yasuhiro Murata ◽  
Keigo Kawashima ◽  
Knvul Sheikh ◽  
Yasuhito Tanaka ◽  
Masanori Isogawa
Keyword(s):  
T Cells ◽  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
Antigen Presentation ◽  
Hematopoietic Cells ◽  
T Cell Responses ◽  
Cross Presentation ◽  
Cell Responses ◽  
B Virus

ABSTRACTCD8+T cells are the key cellular effectors mediating the clearance of hepatitis B virus (HBV) infections. However, early immunological events surrounding the priming of HBV-specific CD8+T cell responses remain poorly understood. This study examined the importance of priming location and the relative contribution of endogenous antigen presentation by hepatocytes versus cross-presentation by bone marrow-derived cells to the induction of functional HBV-specific CD8+T cell responses using the animal models of acute and chronic HBV infection. Functional HBV-specific CD8+T cell responses could be induced to intrahepatically expressed HBV even when T cell homing to the lymphoid tissues was severely suppressed, suggesting that functional priming could occur in the liver. The expansion of HBV-specific CD8+T cells was significantly reduced in the mice whose major histocompatibility complex (MHC) class I expression was mostly restricted to nonhematopoietic cells, suggesting the importance of cross-presentation by hematopoietic cells in the induction of HBV-specific CD8+T cells. Strikingly, the expansion and cytolytic differentiation of HBV-specific CD8+T cells were reduced even more severely in the mice whose MHC class I expression was restricted to hematopoietic cells. Collectively, these results indicate that cross-presentation is required but relatively inefficient in terms of inducing the cytolytic differentiation of HBV-specific CD8+T cells by itself. Instead, the expansion and functional differentiation of HBV-specific CD8+T cells are primarily dependent on hepatocellular antigen presentation.IMPORTANCEHepatitis B virus (HBV) causes acute and chronic hepatitis. Approximately 260 million people are chronically infected with HBV and under an increased risk of developing cirrhosis and hepatocellular carcinoma. Host immune responses, particularly HBV-specific CD8+T cell responses, largely determine the outcome of HBV infection. It is widely accepted that antigen inexperienced CD8+T cells should be initially activated by professional antigen-presenting cells (pAPCs) in lymphoid tissues to differentiate into effector CD8+T cells. However, this notion has not been tested for HBV-specific CD8+T cells. In this study, we show that HBV-specific CD8+T cell responses can be induced in the liver. Surprisingly, antigen presentation by hepatocytes is more important than cross-presentation by hematopoietic cells for the induction of HBV-specific CD8+T cell responses. These results revealed a previously unappreciated role of antigen presentation by hepatocytes in the induction of HBV-specific CD8+T cell responses.

IFN-g-Stimulated Mesenchymal Stromal Cells Acquire the Ability To Cross-Present Exogenous Soluble Antigens and Lead to an Effective Immune Response.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4898-4898
Author(s):  
Moïra François ◽  
Raphaëlle Romieu-Mourez ◽  
Sophie Stock-Martineau ◽  
Jacques Galipeau
Keyword(s):  
Immune Response ◽  
Antigen Presentation ◽  
Mhc Class I ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Class I ◽  
Hybridoma Cells ◽  
Cross Presentation ◽  
Mhc Class I Molecules

Abstract Antigen cross-presentation is the mechanism by which exogenous antigens can be presented by major histocompatibility complex (MHC) class I molecules to CD8+ T cells. This process is efficiently performed by professional antigen presenting cells (APC) such as dendritic cells and macrophages. Recently, we and others have shown that IFN-g enables the upregulation of the expression of MHC class I & II molecules by marrow-derived Mesenchymal Stromal Cells (MSCs) and that MHC II-mediated antigen presentation can lead to cell-mediated protective immunity to xenoantigens [Stagg et al., Blood March 2006]. These findings led us to investigate whether MSCs also possess the ability to cross-present antigens via MHC class I. Using antigen presentation assays performed on murine MSC in the presence of MHC class I-restricted ovalbumin (OVA)-specific CD8+ T hybridoma cells or purified primary CD8+ T lymphocytes from OT1 transgenic mice, we demonstrated that MSC can robustly and effectively cross-present exogenous antigens via MHC class I molecules upon IFN-g pre-treatment in a manner comparable to professional APCs like macrophages. Use of transporter associated with antigen processing (TAP-1)-deficient mice and proteasome inhibitors suggested a MHC class I machinery-dependent pathway. Cross-presentation by IFN-g-activated MSC was also observed to be suppressed by TGF-b and regulated by cell density. In vivo, IFN-g-treated, OVA-pulsed MSCs administered to normal C57Bl/6 mice led to an effective OVA-specific, T cell cytotoxic immune response, leading to the rejection of OVA-expressing EG7 lymphoma cells. In conclusion, our findings suggest that cross-presentation properties of MSC could play a role in their effectiveness as conditional APCs in vivo and this property may be exploited as a therapeutic cell-based immune biopharmaceutical for treatment of cancer or infectious disease.

Sign in / Sign up

Export Citation Format

Share Document