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Antigen Presentation #3: MHC Class I

08 Dec

Antigen Presentation

Presentation by Epithelial Cells

Consider: Under what circumstances would any cell in the body need to initiate an immune response?

Here, I’m using epithelial cells as an example, however, every cell in the body has the ability to present antigens on MHC Class I. In fact, it is a normal, continuous process that the cells cannot fail in without consequence.

While professional APCs process and present antigens that they have phagocytized, other cells divert a small amount of the total protein they make towards MHC I presentation. This allows the immune system to constantly observe these cells and ensure that they are not suffering gross mutations or infections. Most of the time, cells produce normal, ‘self’ proteins against which there are no T Cells (due to negative selection – see Lymphocyte Development).

In the event that MHC I expression is subverted, these cells are presumed to be infected and will be targeted for killing by special cells called Natural Killers, or NK Cells.

If a Non-Self antigen is presented by MHC I, these are recognized by CD8 T Cells. Like the reactions between APCs and CD4 T Cells, cells expressing MHC I + Non-Self Ag engage T Cells via their unique TCRs. The only difference is that these T Cell : Presenting-cell complexes are stabilized by CD8 molecules on CD8+ Killer T Cells.

ImageThe result of this binding is the activation and proliferation of Killer T Cells that will turn upon and kill the presenting cells by releasing perforin and granzymes that perforate target cells and trigger apoptosis (cellular suicide).

Keep in Mind the Big Picture!

To summarize with an example:

  1. Host cells are infected with a virus
  2. The virus replicates within the host cell, producing viral proteins in the process
  3. Some of these proteins are diverted to proteases that digest them and load the antigen fragments onto MHC I molecules
  4. The MHC I +Ag is transported to the plasma membrane to ‘present’ Ag
  5. MHC I +Ag is recognized by a T Cell bearing an TCR specific for the MHC+Ag complex. This interaction is stabilized by CD8 binding to MHC I.
  6. If a stable interaction is formed, the T Cell will become activated, meaning it will proliferate and secrete perforin and granzyme toward the presenting cell
  7. Perforin and Granzyme will lead to the apoptotic death of the presenting cell
  8. By killing the infected cells, the infection can be stopped before spreading farther in the body.

A CD8 T Cell (the smaller cell) killing a virally infected host cell:

Image

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Posted by on December 8, 2013 in Uncategorized

 

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