T cell selection

Definition

Target type: biologicalprocess

The process in which T cells that express T cell receptors that are restricted by self MHC protein complexes and tolerant to self antigens are selected for further maturation. [ISBN:0781735149, PMID:12414722]

T cell selection is a critical process that ensures the development of a functional and self-tolerant T cell repertoire. It occurs in the thymus, a primary lymphoid organ, and involves a series of checkpoints that eliminate T cells that are either self-reactive or unable to recognize foreign antigens.

The process begins with the generation of a diverse pool of T cells in the thymus, where progenitor cells undergo V(D)J recombination to generate a wide array of unique T cell receptors (TCRs). These TCRs are expressed on the surface of immature T cells, known as thymocytes.

**Positive Selection:** The first checkpoint, positive selection, ensures that T cells are able to recognize and bind to self-MHC molecules. This process occurs in the thymic cortex, where thymocytes interact with cortical epithelial cells expressing MHC molecules. Only thymocytes that can bind to MHC molecules with sufficient affinity survive. This ensures that T cells are capable of recognizing antigens presented by MHC molecules, which are essential for immune responses.

**Negative Selection:** The second checkpoint, negative selection, eliminates T cells that are self-reactive, meaning they can recognize and bind to self-antigens presented by MHC molecules. This process occurs in the thymic medulla, where thymocytes interact with medullary epithelial cells, dendritic cells, and macrophages that present a diverse array of self-antigens. Thymocytes that bind too strongly to self-antigens undergo apoptosis, ensuring that the immune system does not attack the body's own tissues.

**T Cell Differentiation:** After positive and negative selection, surviving thymocytes differentiate into either CD4+ helper T cells or CD8+ cytotoxic T cells, depending on the type of MHC molecule they recognize. CD4+ T cells recognize MHC class II molecules, which present antigens derived from extracellular sources, while CD8+ T cells recognize MHC class I molecules, which present antigens derived from intracellular sources.

**Peripheral Tolerance:** Even after passing through thymic selection, some self-reactive T cells may escape into the periphery. Mechanisms of peripheral tolerance, such as regulatory T cells (Tregs) and anergy, help to suppress the activity of these potentially autoreactive T cells.

In summary, T cell selection is a complex and multi-step process that ensures the development of a T cell repertoire that is both functional and self-tolerant. This process is essential for a healthy immune system and prevents the development of autoimmune diseases.'
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Compounds (3)