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Quick Question about MHC's


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I'm pretty sure that all cells express MHCI; for dendritic cells (and probably macrophages), the MHCII expression level is a function of the activation state of the cell. So not all dendritic cells express MHCII.

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which of the following situation would have antigens presented in MHCIIs for dendritic cells?

 

 

the situation where the dendritic cells that are only endocytosed the antigen but not hijacked?

 

or

 

dendritic cells that have been actually infected the antigen and have their molecular machinery hijacked?

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Actually, I wasn't entirely truthful about the MHCII expression on dendritic cells before. Naive (unactivated) dendritic cells express MHCII to a very low extent. In this state, when the dendritic MHCII presents antigen to a T cell, and the T cell recognizes it, the dendritic cell figures that the T cell is recognizing "self" antigen - that is, the T cell wants to kill your own cells. So the dendritic cell signals that T cell to kill itself.

 

However, when the dendritic cell gets a signal that an infection is ongoing (ie, DNA containing CpG repeats = viral infection; lipopolysaccharide = bacterial infection), it starts expressing a lot of MHCII and endocytosing a lot of foreign antigen to present. These "activated" dendritic cells don't kill the T cells, they activate them. And the activated T cells activate B cells in turn.

 

So, by the most circuitous route possible, to answer your question, MHCIIs only present endocytosed antigen. However, many viruses (and bacteria?) have evolved to take advantage of the endocytosis route. Influenza virus, for one, signals the cell to endocytose the virus particle. When the endocytosed vacuole (containing the virus) becomes acidified in the process of forming a lysosome, the pH change causes a protein in the flu virus's envelope to change shape and fuse the virus envelope with the lysosome envelope, thus releasing the viral genome into the cytosol. I don't know offhand if any viruses have specifically taken advantage of the dendritic/macrophage endocytosis process, but I'm sure some have. So the answer to your question would be yes to both, but in most situations, the dendritic cell is presenting antigen without actually being infected.

 

Sorry to go on so long, but this is what I do at my job. I actually just injected a bunch of mice today with artificially activated dendritic cells.

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Zyncod, so what you are saying is that the dendritic cells actually have the ability to kill T-cells? If so, would you know where to find information on the signaling mechanism? So unless the T-Cell is activated, it will just keep on going killing dendritic cells?

 

I understand your little tid-bit about the MHCII presenting antigen part, thanks.

 

Also, just to double check, when the dendritic cells have been infected by viral particles, the cell presents its own antigens via only the MHCI (as opposed to MHCII) mechanism?

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Dendritic cells can kill T cells, in order to protect the T cells from attacking the body. T cells can kill dendritic cells, but really only if the dendritic cells are infected or the person has an autoimmune problem like lupus. I think that the dendritic cells induce apoptosis in the T cells, so they probably act through the Fas pathway. Here's a paper about dendritic cells and T cell tolerogenesis:

Gad M, Claesson MH, Pedersen AE. Dendritic cells in peripheral tolerance and immunity. APMIS

2003;111:766–75.

 

And yes, when DCs are infected, they present their cytosolic antigens by MHCI.

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