Antigen cross‐presentation: proteasome location, location, location

Desjardins, Michel

doi:10.15252/embj.2019102799

Cited by 4 publications

(4 citation statements)

References 9 publications

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“…Endogenous antigens and cross-presented exogenous antigens went through cytoplasmic ubiquitin–proteasome degradation, followed by MHC class I- and II-restricted presentation that eventually activated CD8+ and CD4+ T cells . The enhanced cell uptake and specific localization on the ER of antigen enhanced the activation of BMDCs.…”

Section: Resultsmentioning

confidence: 99%

“…Endogenous antigens and cross-presented exogenous antigens went through cytoplasmic ubiquitin− proteasome degradation, followed by MHC class I-and IIrestricted presentation that eventually activated CD8+ and CD4+ T cells. 28 The enhanced cell uptake and specific localization on the ER of antigen enhanced the activation of BMDCs. As shown in Figures 3a,b and S3, OVA@LIPO exerted a weak promoting effect, while OVA-loaded targeting LIPO, especially OVA@PM-LIPO, significantly upregulated the expression of MHC-II and CD80 molecules.…”

Section: Pm-lipo-mediatedmentioning

confidence: 99%

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Liposome Vaccine for Active Regulation of Cellular and Humoral Immunity

Luo,

Wang

et al. 2023

Mol. Pharmaceutics

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Despite significant progress in vaccine development, especially in the fight against viral infections, many unexplored areas remain including innovative adjuvants, diversification of vaccine formulations, and research into the coordination of humoral and cellular immune mechanisms induced by vaccines. Effective coordination of humoral and cellular immunity is crucial in vaccine design. In this study, we used the spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or ovalbumin (OVA) as antigen models and CpG DNA (an activator of toll-like receptor 9, TLR9) as an adjuvant to prepare a multitargeted liposome (LIPO) vaccine. Once equipped with the ability to target lymph nodes (LN) and the endoplasmic reticulum (ER), the LIPO vaccine significantly enhances the cross-presentation ability of antigen-presenting cells (APCs) for exogenous antigens through the ER-associated protein degradation (ERSD) mechanism. Additionally, the vaccine could fine-tune the efficiency of ER-targeted antigen delivery, actively regulating the presentation of exogenous antigen proteins via the major histocompatibility complex (MHC-I) or MHC-II pathways. Immune data from in vivo mouse experiments indicated that the LIPO vaccine effectively stimulated both humoral and cellular immune responses. Furthermore, it triggers immune protection by establishing a robust and persistent germinal center. Moreover, the multifunctionality of this LIPO vaccine extends to the fields of cancer, viruses, and bacteria, providing insights for skilled vaccine design and improvement.

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Section: Resultsmentioning

confidence: 99%

Section: Pm-lipo-mediatedmentioning

confidence: 99%

Liposome Vaccine for Active Regulation of Cellular and Humoral Immunity

Luo,

Wang

et al. 2023

Mol. Pharmaceutics

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“…Up to about 60% of mouse specific peptides in the PDX models fitted the patients' HLA peptide binding motif ( supplemental Table S2 ). This could be because of overlap between the binding motifs of the patients and of the mice or may suggest that mouse peptides might have been loaded exogenously by cross presentation onto the HLA molecules of the human tumors grafted in mice ( 87 , 88 ). An interesting point is the similar distribution of the NetMHCpan ranks of the mouse-only peptides compared with the NetMHCpan ranks of the human HLA peptides.…”

Section: Discussionmentioning

confidence: 99%

Identification of Tumor Antigens in the HLA Peptidome of Patient-derived Xenograft Tumors in Mouse

Rijensky

Shraga

Barnea

et al. 2020

Molecular & Cellular Proteomics

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Personalized cancer immunotherapy targeting patient-specific cancer/testis antigens (CTA) and neoantigens may benefit from large-scale tumor human leukocyte antigen (HLA) peptidome (immunopeptidome) analysis, which aims to accurately identify antigens presented by tumor cells. While significant efforts have been invested in analyzing the HLA peptidomes of fresh tumors, it is often impossible to obtain sufficient volumes of tumor tissues for comprehensive HLA peptidome characterization. This work attempted to overcome some of these obstacles by using patient-derived xenograft tumors (PDX) in mice as the tissue sources for HLA peptidome analysis. PDX tumors provide a proxy for the expansion of the patient tumor by re-grafting them through several passages to immune-compromised mice. The HLA peptidomes of human biopsies were compared to those derived from PDX tumors. Larger HLA peptidomes were obtained from the significantly larger PDX tumors as compared to the patient biopsies. The HLA peptidomes of different PDX tumors derived from the same source tumor biopsy were very reproducible, even following subsequent passages to new naïve mice. A large number of CTA-derived HLA peptides were discovered, as well as several potential neoantigens/variant sequences. Taken together, the use of PDX tumors for HLA peptidome analysis serves as a highly expandable and stable source of reproducible and authentic peptidomes, opening up new opportunities for defining large HLA peptidomes when only small tumor biopsies are available. This approach provides a large source for tumor antigens identification, potentially useful for personalized immunotherapy.

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“…CD8+ T cells can detect viral antigens presented through MHC class I molecules on infected cells or on DCs. The antigens can be endogenously from viral encoded proteins and are presented directly or they are derived exogenously from phagocytosed viral particles resulting in cross-presentation [130]. Detection of viral antigens by CD8+ T cells results in the destruction of the cell by induction of apoptosis [131].…”

Section: Sars-cov-2mentioning

confidence: 99%

Virus-host interactions resolved through manipulation of viral and host gene expression

Buhr¹

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Antigen cross‐presentation: proteasome location, location, location

Cited by 4 publications

References 9 publications

Liposome Vaccine for Active Regulation of Cellular and Humoral Immunity

Liposome Vaccine for Active Regulation of Cellular and Humoral Immunity

Identification of Tumor Antigens in the HLA Peptidome of Patient-derived Xenograft Tumors in Mouse

Virus-host interactions resolved through manipulation of viral and host gene expression

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