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The
Role of the Class I and II Major Histocompatibility Complexes (MHC)
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The
T cell is one of the most important elements in the human immune system.
Its role in directly destroying infected or cancerous cells is great,
and it is the control center for the rest of the acquired and innate
immune system. The numerous cytokines it produces and its array of
surface molecules are critical for the control of all other immune
elements.
There are two types of T cells; cytotoxic T cells (CTL) and T helper
cells. CTL act as guardians against cellular change (tumors, invasion
by viruses). T helper cells orchestrate immune responses to extracellular
pathogens. The destruction of the T helper cell lineage results in
the total collapse of the immune system, as illustrated by HIV/AIDS.T
cells do not act in isolation from other components of the immune
system.
Many other cell types including macrophages, NK cells, and B cells
are important in the effector phase of the immune response. Macrophages
and dendritic cells are also important regulators of immune response,
especially since they are generally responsible for processing and
presenting antigens (molecules that stimulate immune response) to
T cells.
The elements on these antigen presenting cells (APC) and some other
cells which are central to the control of T cells are the Major Histocompatibility
Complex (MHC) molecules. MHC molecules present processed internal
or external antigens to the T cell. Their concentration on a cell
surface is a critical determinant of the degree of T cell activation.
And, as their name suggests, they contribute to the T cell's ability
to discriminate between self and other. |
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| MHC
I Expression and Peptide Processing |
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A
small percentage of all the proteins inside the cytosol of a cell
are degraded by a Low Molecular Weight Protease (LMP) and moved
from the cytoplasm to the rough endoplasmic reticulum (RER) by the
Transporter of Antigenic Peptides (TAP)protein.
Inside the RER some of these peptides, which are approximately ten
amino acids in length, will associate with the alpha-1 and alpha-2
proteins of MHC class I. The peptide must be able to bind to the
cleft between the alpha-1 and alpha-2 domains of the molecule and
result in a conformational change which allows for the association
of the beta-2 microglobulin, or the MHC molecule will destabilize
and not be expressed on the cell surface. Peptides which meet this
requirement form a complex with the MHC Class I molecule. This complex
is transported in a vesicle from the RER to the Golgi Body and from
there to the surface of the cell. With the exception of neurons,
all somatic nucleated cells express MHC Class I on their surfaces.
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