User:Immcarle82/sandbox

Outline and Draft for Article:

General information seems alright -- but could still expand

Cross-presentation is the ability of certain antigen-presenting cells to take up, process and present extracellular antigens with MHC class I molecules to CD8 T cells(cytotoxic T cells). Cross-priming, the result of this process, describes the naive cytotoxic CD8⁺ T cell stimulation. This process is necessary for immunity against most tumors and against viruses that do not readily infect antigen-presenting cells, or impair dendritic cell normal function . It is also required for induction of cytotoxic immunity by vaccination with protein antigens, for example, tumour vaccination.

Cross-presentation is of particular importance, because it permits the presentation of exogenous antigens, which are normally presented by MHC II on the surface of infected dendritic cells to be also presented by MHC I without infecting the dendritic cell. Cross-presentation allows the dendritic cell to avoid using the endogenous proteasomal processing pathway, which otherwise would divert cellular resources away from MHC II presentation processes that present exogenous antigens after infection. Such a diversion could functionally impair the dendritic cell.

Contents

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• 1History
• 2Relevance for immunity
• 3Relevance for immune tolerance
• 4Cell biology
• 5Cytosolic Diversion
• 6References
• 7External links

History[edit] -- Expand History

The first evidence of cross-presentation was reported in 1976 by Michael J. Bevan after injection of cells carrying alloantigens into experimental animals. This resulted in CD8 T cell responses that were induced by antigen-presenting cells of the recipient, implying that these must have taken up and processed the injected cells. This observation was termed “cross-priming”.

Later, there had been much controversy about cross-presentation, which now is believed to have been due to particularities and limitations of some experimental systems used.

Relevance for immunity[edit] -- Expand Role in immunity

Cross-presentation has been shown to play a role in the immune defense against many viruses (herpesvirus, influenzavirus, CMV, EBV, SIV, papillomavirus, and others), bacteria (listeria, salmonella, E. coli, M. tuberculosis, and others) and tumors (brain, pancreas, melanoma, leukemia, and others). Even though many viruses can inhibit and degrade dendritic cell activity, cross-presenting dendritic cells that are unaffected by the virus are able to intake the infected dendritic cell and still cross present the antigen to T cells. The action of cross priming can bolster immunity against antigens that target dendritic cells in order to inhibit maturation and an immune response from T cells.

Cross-priming avoids viral immune evasion strategies, such as suppression of antigen processing. Consequently, immune responses against viruses that are able to do so, such as herpes viruses, are largely dependent on cross-presentation.

Relevance for immune tolerance[edit]

Some self-antigens (autoantigens) are cross-presented, resulting in the elimination of autoreactive CD8 T cells. This mechanism to maintain self tolerance has been termed cross-tolerance.

Cell biology[edit] ---- Change Section to Molecular Pathways of Cross Presentation -- Include Cytosolic and Vacuolar Pathway

ntigen-presenting cells capable of cross-presentation are primarily dendritic cells, but macrophages, B lymphocytes and sinusoidal endothelial cells have also been shown to be able to do so. The intracellular mechanisms of cross-presentation are still unclear, but seem to involve specialized subcellular compartments bearing characteristics of both the endoplasmic reticulum and the endosome.

Endocytosed proteins are transported out of this compartment into the cytoplasm by unknown mechanisms. There they are processed by the proteasome into peptides, which are transported by the TAP transporter into the endoplasmic reticulum, or back into the same endosomes, where they associate with MHC I. In addition to solid structure uptake, dendritic cell phagocytosis simultaneously modifies the kinetics of endosomal trafficking and maturation. As a consequence, external soluble antigens are targeted into the MHC class I cross-presentation pathway.

According to another study (done by some of the same people cited at the bottom of paragraph 1 of this section), as the phagosome forms or soon after it forms, it fuses with the ER to form an ER-phagosome mix compartment. The ATP-dependent TAP of the phagosomal compartment (at some stage of its lifecycle) transports the antigens out to the cytosol for proteasomal degradation and back into the compartment for loading onto MHC I. This mix compartment set-up helps the cell tolerate the scarcity of antigens in the relatively large cytoplasm for cross-presentation.

Finally, MHC class I-peptide complexes are transported to the cell surface, where they can be detected by specific CD8 T cells.

Figure for Molecular Pathways of Cross Presentation:

Cytosolic Diversion[edit]

There is evidence that suggest that cross-presentation requires cytosolic diversion in a proportion of CD8(+) dendritic cells that are able to cross-present.

In the capable dendritic cells, cytosolic diversion is the name of the process that diverts antigens away from the route in which they are guided for antigen presentation by MHC II by being transported for release into the cytoplasm following endocytosis for degradation by the proteasomes necessary for MHC I antigen presentation (cross-presentation).

There is evidence that phagosome-to-cytosol diversion (cytolic diversion) of endocytosed ovalbumin antigens (OVA) occur in Archaea, after which classical antigen processing for presentation by MHC I occurs. The process of endocytosis and cross-presentation (involving cytosolic diversion) can be enhanced by the addition of an adjuvant in the form of isoprenoid glycerolipid vesicles named archaeosomes and filled with the antigens. The adjuvant is recognized by phosphatidylserine receptors.

Updated Sources for Article Edit:

1. Gutiérrez-Martínez et al. 2015. Cross-presentation of cell-associated antigens by MHC class I in dendritic cell subsets.

2. Joffre et al. 2012. Cross Presentation by Dendritic Cells. Nature Reviews

3. Amigorena and Savina, 2010. Intracellular mechanisms of antigen cross presentation in dendritic cells.

4. Sathe et al. 2011. The Acquisition of Antigen Cross-Presentation Function by Newly Formed Dendritic Cells

5. Nair-Gupta et al. 2014. TLR Signals Induce Phagosomal MHC-I Delivery from the Endosomal Recycling Compartment to Allow Cross-Presentation

Plan For Article Edit:

First and foremost, I plan on making sure that all sources within the article are properly sourced. There are many outdated sources within the article, and I plan on updating the research time frame for cross presentation. Currently, there doesn't appear to be a section that is currently missing from the article, but there definitely does appear to be a lack of depth in the present sections. Because of this, I plan on expanding the article as a whole by going in depth on the various outlined sections of the article. By expanding the individual parts within the article, I believe that I will add more depth and research knowledge to the article on cross presentation as a whole.

Article Evaluation:

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  • The article appears neutral and is simply trying to describe cross-presentation.
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  • Many topics appear underrepresented -- only the Cell Biology section appears to be sufficient.
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  • Sources appear to work, are relatable, and seem updated
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  • Some facts and statements appear to need to be sourced. But, for the most part -- It looks all good.
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  • Definitely could use supplemental information in almost all sections -- But the research appears to be up to date.
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  • We haven't gotten to this particular portion of antigen presentation. But all of the terms we have used in class are coming up in the article.

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