MHC restriction

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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 particular 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 differentiation 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 or 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.

Eventually, 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.