Where does negative selection of T cells primarily occur?

Negative selection of T cells primarily occurs in the medulla of the thymus, which plays a crucial role in ensuring that the immune system is properly self-tolerant. During this process, developing T cells, or thymocytes, are exposed to self-antigens presented by medullary thymic epithelial cells. Those thymocytes that bind too strongly to self-antigens are induced to undergo apoptosis, or programmed cell death, thereby eliminating T cells that could potentially target the body’s own tissues and cause autoimmune diseases.

The medulla, therefore, serves as a critical environment for honing the T cell repertoire to maintain self-tolerance while allowing for the survival of T cells that can effectively respond to foreign pathogens. The role of the medulla in negative selection is vital as it helps to prevent autoimmune reactions and contributes to the overall regulation of immune responses.

While the cortex of the thymus is involved in positive selection, which ensures that T cells can adequately recognize self-MHC molecules, the definitive action of removing potentially auto-reactive T cells primarily takes place in the medulla. Thus, emphasizing the specific role of the medulla in the thymus is key to understanding T cell development and the mechanisms of immune tolerance.