Thymic Selection

∞ generated and posted on 2016.12.11 ∞

Removal by the body of T cells that are unable to recognize major histocompatibility complex molecules or which are able to recognize self antigens.

An effectively infinite number of T cell variants are created by the body within bone marrow but then have to winnowed down to those which are sufficiently functional (thus able to bind to major histocompatibility complex) but not too functional (thus unable to recognize self antigens, thereby avoiding autoimmunity). Thymic selection accomplishes both of these tasks.

Thymic selection can be differentiated into stages of positive thymic selection and negative thymic selection. Both are required for successful T cell maturation. Contrast with clonal selection as seen with both B cells and T cells and which occurs, for T cells, following thymic selection.

Positive thymic selection is selection for those immature T cells that are able to recognize major histocompatibility complex (MHC) molecules. The basis of this selection is that the raison d'être of T cells is MHC recognition. Since T cells differ in part in terms of their T-cell receptors, which are the proteins that recognize MHC, a substantial fraction of T cell variants, that is, T-cell clones, fail to achieve that basic ability so are eliminated via positive thymic selection.

Negative thymic selection starts with those T cells that have passed positive thymic selection. At this point all of the remaining T cells can recognize MHC and the goal of negative thymic selection is to remove those clones that are able to recognize self antigens that are displayed by MHC (keeping in mind that MHC doesn't "care" what the source is of the antigens it displays, i.e., self or foreign antigen, but that this distinction between self and foreign instead is made by the T cells and their receptors, i.e., as a consequence of negative thymic selection). See clonal deletion for the equivalent process with B cells.

The reason for this second step is that, without it, autoimmune disease will result, i.e., as tissues that are recognized by T cells will be eliminated via the action or consequence of cytotoxic T cells, antibody binding, and natural killer cells. As a result, still maturing T cells are exposed to the plethora of self antigens that can be complexed with MHC, and those T cells that bind self-associated MHC are deleted, that is, subject to apoptosis.

Thymic selection takes place in the thymus and approximately 2% of the original, immature T cells survive this process. Resulting from this selection are populations of T-cell clones, each of which has a potential to recognize, as complexed with MHC, many foreign, i.e., exogenous antigens, but not self antigens.

The majority of T-cell clones actually will never recognize foreign antigens since the body generates an oversupply of T cell as well as B cell diversity. Most of this diversity is never used but nonetheless is held in reserve for when the body is exposed to otherwise unrecognized pathogens.