What are the positive and negative selection of T cells?

Positive and negative selection are two processes that are an integral part of T cell development. 

T cells, which are a part of the adaptive immune response, play a vital role in protecting our bodies against foreign pathogens. This ability depends largely on the T cell’s ability to recognize pathogens and distinguish between self or non-self cells. This ability to recognize and distinguish between self and on-self cells is how T cells identify and attack invading pathogens while leaving self-cells unharmed. The processes of positive and negative selection ensure that T cells have this capability. 

Positive selection

Positive selection ensures that T cells are able to bind MHC complexes. It takes place in the thymus. 

During positive selection, thymic cells present short fragments of proteins, called peptides, on their own MHC class I and MHC class II molecules. If the TCR (T cell receptor) of a T cell successfully binds to the MHC complexes on the thymic cells, the T cell receives survival signals. This means it is positively selected. 

The positive selection process also determines if a T cell will become a CD8+ (cytotoxic) T cell or a CD4+ (helper) T cell. If a TCR complex binds strongly to MHC class II, that T cell differentiates into a helper or CD4+ T cell. If a TCR does not bind strongly to MHC class II, that T cell differentiates into a cytotoxic or CD8+ T cell. 

The positive selection of T cells results in the development of mature CD8+ (cytotoxic) T cells and CD4+ (helper) T cells capable of recognizing MHC complexes.

Negative selection

The ability of T cells to recognize antigen-MHC complexes is integral to their ability to eliminate infection-causing pathogens. However, it is just as important to ensure that T cells do not recognize and attack the organism’s own cells. This is the main purpose of negative selection. 

During negative selection, immature T cells that bind too strongly to the MHC complexes are destroyed. This is because when a TCR binds too strongly to the MHC complex, it is more likely to become self-reactive and attack the organism’s own cells. The potentially harmful T cells are destroyed through the process of apoptosis. 

Positive selection of T cells occurs first and is followed by negative selection. The T cells that leave the thymus at the end of the negative selection process are self-restricted and self-tolerant.