MHC restriction
Encyclopedia
MHC-restricted antigen recognition, or MHC restriction, refers to the fact that a given T cell
will recognize a peptide
antigen
only when it is bound to a host bodies' own MHC
molecule. Normally, as T cells are stimulated only in the presence of self-MHC molecules, antigen is recognized only as peptides bound to self-MHC molecules.
MHC restriction is particularly important when primary lymphocytes are developing and differentiating in the thymus
or bone marrow
. It is at this stage that T cells die by apoptosis if they express high affinity for self-antigens presented by an MHC molecule or express too low affinity for self MHC. This is ensured through two distinct developmental stages: positive selection and negative selection.
Developing T cells in the primary lymphoid organs (thymus) first express neither CD4, CD8 nor TcR (T cell receptor). This is referred to as double negative selection. After differentiation, the T cell expresses both CD4
, CD8
and TcR
. This is referred to as double positive selection. It is at this stage that select T cells undergo apoptosis if they are found to select for self-antigen. This is a necessary step as it prevents T cells from cascading an autoimmune response
against its host tissues.
Ultimately, the T cells differentiate and mature to express either CD4 and TcR or CD8 and TcR. At this point the T cells leave the primary lymphoid organ and enter the blood stream.
Conversely, it is thought that MHC Restriction plays a pivotal role in the antiretroviral therapy used to treat HIV/AIDS as it can increase the CD4 cell count thus increasing the likelihood for an immune response to be prompted.
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
will recognize a peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
only when it is bound to a host bodies' own MHC
Major histocompatibility complex
Major histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...
molecule. Normally, as T cells are stimulated only in the presence of self-MHC molecules, antigen is recognized only as peptides bound to self-MHC molecules.
MHC restriction is particularly important when primary lymphocytes are developing and differentiating in the thymus
Thymus
The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....
or bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
. It is at this stage that T cells die by apoptosis if they express high affinity for self-antigens presented by an MHC molecule or express too low affinity for self MHC. This is ensured through two distinct developmental stages: positive selection and negative selection.
Developing T cells in the primary lymphoid organs (thymus) first express neither CD4, CD8 nor TcR (T cell receptor). This is referred to as double negative selection. After differentiation, the T cell expresses both CD4
CD4
CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984...
, CD8
CD8
CD8 is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor . Like the TCR, CD8 binds to a major histocompatibility complex molecule, but is specific for the class I MHC protein. There are two isoforms of the protein, alpha and beta, each encoded by a different gene...
and TcR
T cell receptor
The T cell receptor or TCR is a molecule found on the surface of T lymphocytes that is responsible for recognizing antigens bound to major histocompatibility complex molecules...
. This is referred to as double positive selection. It is at this stage that select T cells undergo apoptosis if they are found to select for self-antigen. This is a necessary step as it prevents T cells from cascading an autoimmune response
Autoimmunity
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...
against its host tissues.
Ultimately, the T cells differentiate and mature to express either CD4 and TcR or CD8 and TcR. At this point the T cells leave the primary lymphoid organ and enter the blood stream.
Conversely, it is thought that MHC Restriction plays a pivotal role in the antiretroviral therapy used to treat HIV/AIDS as it can increase the CD4 cell count thus increasing the likelihood for an immune response to be prompted.