T cell receptor V(D)J recombination

Definition

Target type: biologicalprocess

The process in which T cell receptor V, D, and J, or V and J gene segments, depending on the specific locus, are recombined within a single locus utilizing the conserved heptamer and nonomer recombination signal sequences (RSS). [GOC:add, ISBN:0781700221]

T cell receptor (TCR) V(D)J recombination is a crucial process in the development of a functional and diverse T cell repertoire. It involves the rearrangement of gene segments encoding the TCR, a cell surface receptor responsible for recognizing and responding to specific antigens presented by antigen-presenting cells. This intricate process occurs in developing T cells within the thymus, a primary lymphoid organ.

The TCR is composed of two polypeptide chains: an α chain and a β chain. Each chain consists of a variable (V) region responsible for antigen recognition and a constant (C) region involved in signal transduction. The V region of each chain is generated through a series of DNA rearrangements involving multiple gene segments.

**V(D)J recombination:**

- **V, D, and J gene segments:** The TCR α chain is encoded by V and J gene segments, while the TCR β chain is encoded by V, D, and J gene segments. These gene segments are arranged in tandem arrays on chromosomes 14 (α chain) and 7 (β chain).
- **RAG1/2 enzymes:** The process is initiated by the RAG1 and RAG2 enzymes, which are specifically expressed in developing T cells. RAG1/2 recognize specific DNA sequences called recombination signal sequences (RSSs) flanking each V, D, and J segment.
- **DNA cleavage and joining:** RAG1/2 enzymes introduce double-stranded breaks at the RSSs, resulting in the excision of intervening DNA. The broken ends are then processed by other enzymes, such as DNA-dependent protein kinase (DNA-PK) and Artemis. The processed ends are subsequently joined together by the non-homologous end-joining (NHEJ) pathway, which involves several enzymes including Ku70/80, DNA ligase IV, and XRCC4.
- **Diversity generation:** The random selection and rearrangement of V, D, and J gene segments, along with the addition of non-templated nucleotides (N-nucleotides) during the joining process, generate an enormous diversity of TCRs. The diversity generated by V(D)J recombination is crucial for recognizing a vast array of antigens.

**T cell development and selection:**

- **Positive selection:** T cells that express TCRs capable of recognizing self-MHC molecules are positively selected and allowed to survive.
- **Negative selection:** T cells that express TCRs that bind strongly to self-antigens are negatively selected and eliminated, preventing autoimmune responses.

**Significance:**

- **Immune repertoire:** V(D)J recombination generates a vast repertoire of T cells, each with a unique TCR capable of recognizing a specific antigen.
- **Adaptive immunity:** The ability to generate TCRs specific for diverse antigens enables the adaptive immune system to mount targeted responses against invading pathogens.
- **Immunological memory:** Memory T cells generated during a primary immune response can rapidly respond to subsequent encounters with the same antigen.

V(D)J recombination is a complex and highly regulated process that ensures the generation of a diverse and functional T cell repertoire, enabling the immune system to effectively combat infections and maintain immune homeostasis.'
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Proteins (1)

Compounds (46)