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Phagocytic processing of bacterial antigens for class I MHC presentation to T cells
Abstract
Class I major histocompatibility complex (MHC) molecules present antigens that are produced within the presenting cell or penetrate from the vacuolar system into the cytosol for processing. Most studies of exogenous antigen processing have used soluble antigens, which are not efficiently presented by class I MHC molecules and do not elicit CD8 T-cell responses in vivo. But particulate antigen preparations with no known mechanism for cytosolic penetration can also elicit CD8 T-cell responses in vivo. We report here that phagocytosis of bacteria with no mechanism for cytosolic penetration also results in presentation of bacterial antigens by class I MHC molecules. Moreover, this mechanism is resistant to cycloheximide and Brefeldin A, which block the classical class I processing pathway. These results suggest a novel vacuolar class I processing pathway for exogenous phagocytic antigens.
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“We demonstrate that bacterial HLA-I and HLA-II peptides can be presented by both antigen-presenting cells (as has previously been shown25–28) and by melanoma cells”
From Identification of bacteria-derived HLA-bound peptides in melanoma (2021) · cites this paper as [26]
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MHC Class I Antigen Processing Pathways
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“Presentation of exogenous proteins by class I molecules in macrophages is markedly enhanced under conditions favoring uptake of antigen by phagocytosis (54, 56, 57, 64) or macropinocytosis (48).”
BackgroundEscape from the Phagosome: The Explanation for MHC-I Processing of Mycobacterial Antigens?
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“Alternatively, the antigenic protein could be processed and loaded on to MHC-I in an alternate MHC-I pathway that did not require access to the cytosol (25, 36).”
BackgroundResultExogenous antigen targeted to FcγRI on myeloid cells is presented in association with MHC class I
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“Knowledge of bacterial viability within antigen-processing cells is potentially important for antigen presentation, since two distinct mechanisms of presentation by class I major histocompatibility complex molecules have been described (19).”
BackgroundAmorphous silica nanoparticles enhance cross-presentation in murine dendritic cells
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“3 cells, a T–T hybridoma against the OVA257–264/MHC class I molecule (H-2 Kb) complex [21], were kindly provided by Dr.”
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“In addition, the presence of multiple immunogens on each nanoparticle is likely to improve loading on class I MHC molecules as cross-presentation of antigens attached or adsorbed to particles in the 20 nm to 3 μm size range is more efficient than with soluble proteins.(32,33) The role of the inorganic core is less cle…”
Cross-presentation of IgG-containing immune complexes
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“Although both cross-presentation pathways have been well-documented in the past [31,32], most of the published data point to the endosome-to-cytosol pathway as a dominant mechanism of cross-presentation.”
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“The processing pathway of the antigen depends not only on the presence of cleavage and binding sites for the proteasomes or for other antigen-processing enzymes, but also on the availability to these enzymes (endosome/lysosomes versus cytosol, endoplasmic reticulum, or nucleus) (4, 8, 26, 34, 37, 38).”
BackgroundAntigen cross-presentation: extending recent laboratory findings to therapeutic intervention
Flinsenberg, T. W. H., Compeer, E. B., Boelens, J. J., & Boes, M. L. (2011) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2011.04411.x · Cited by 43
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“Ags in a noncharacterized endocytic compartment followed by secretion and loading of antigenic peptides into MHC-I molecules on the macrophages’ cell surface and bystander cells (30, 43).”
BackgroundPhagocytosis and antigen presentation
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Antigen-presenting cells and anti- immunity
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Self-citationAntigen processing mutant T2 cells present viral antigen restricted through H‐2K
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The role of endosomes in innate and adaptive immunity
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“Since antigen processing for MHC class I pathway by antigen-presenting cells infected with Salmonella strains has been demonstrated (37), it is tempting to speculate that an efficient cytotoxic immune response might also be induced by surface-displayed antigens.”
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Self-citationAntigen processing and intracellular traffic of antigens and MHC molecules
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“vacuolar presentation pathway is insensitive to cycloheximide treatment (36).”
BackgroundNo life without death—apoptosis as prerequisite for T cell activation
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MHC Class I-Restricted Presentation of Maleylated Protein Binding to Scavenger Receptors
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“While fluid-phase proteins are processed and presented by APCs of the monocytic lineage for MHC class I-restricted presentation (27), the efficiency of this presentation has been shown to improve markedly if the Ag is taken up by phagocytosis in either Salmonellae (44), Escherichia coli(45), acid-resistant liposomes (…”
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“Alternative pathways of antigen processing and presentation to CTL are an area of current investigation in several laboratories (3, 7, 8, 13, 14).”
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Internalization of Iscom-Borne Antigens and Presentation under MHC Class I or Class II Restriction
Villacres, M. C., Behboudi, S., Nikkila, T., Lövgren-Bengtsson, K., & Morein, B. (1998) · Cellular Immunology · doi:10.1006/cimm.1998.1278 · Cited by 40
The Endoplasmic Reticulum Chaperone GRP170: From Immunobiology to Cancer Therapeutics
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“…presentation) The recent demonstration of successful presentation of exogenous antigens in the context of M HC class I molecules (Rock et al., 1990; Pfeifer et al., 1993) opens the possibility that even the generation of M HC class I-restricted, CDS'*", M-3 specific cytotoxic cells did not occur…”
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“M HC class I molecules monitor the interior of cells for the presence of peptides derived from pathogens such as viruses and intracellular bacteria (1, 2).”
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Metadata
- Authors
- Pfeifer, J. D., Wick, M. J., Roberts, R. L., Findlay, K., Normark, S. J., & Harding, C. V.
- Affiliations
- Washington University in St. Louis (US)
- Venue
- Nature
- Published
- 1993-01
- Volume
- 361
- Issue
- 6410
- Pages
- 359-362
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2042470561
- Cited by
- 615
- References
- 31
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 7 · 2022: 3 · 2021: 6 · 2020: 8 · 2019: 6 · 2018: 8 · 2017: 9 · 2015: 4 · 2014: 8 · 2013: 10 · 2012: 10
- FWCI
- 22.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- MHC class I, antigen processing, phagocytosis, bacterial antigens, CD8+ T cells, exogenous antigen presentation, cycloheximide resistance, particulate antigen
- MeSH terms
- Amino Acid Sequence, Animals, Epitopes, Antigens, Bacterial, Bacterial Proteins, Escherichia coli, Macrophages, Mice, Inbred CBA, Mice, Inbred C57BL, Microscopy, Electron, Molecular Sequence Data, Ovalbumin, Phagocytosis, Recombinant Fusion Proteins, Salmonella typhimurium, T-Lymphocytes, Vacuoles, Histocompatibility Antigens Class I, T-Lymphocyte Subsets, CD8 Antigens, Escherichia coli Proteins, Mice
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