MHC Restriction

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 body's 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. Positive selection ensures that any cells with a high enough affinity for peptide bound MHC survive. Whilst negative selection induces death in cells which bind MHC too strongly. This is not to be confused with 'double positive' or 'double negative' cell phenotypes during T-cell development.

Developing T cells in the primary lymphoid organs (thymus) first express neither CD4, CD8 nor TcR (T cell receptor). These cells are referred to as double negative. After differentiation, the T cell expresses both CD4, CD8 and TcR. These cells are referred to as double positive. 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.