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[7] [17] [18] Although expression is typically found to be in the primary lymphoid organs, recent work has suggested that stimulation via antigen can result in secondary TdT expression along with other enzymes needed for gene rearrangement outside of the thymus for T-cells. [19] Patients with acute lymphoblastic leukemia greatly over-produce ...
V(D)J recombination (variable–diversity–joining rearrangement) is the mechanism of somatic recombination that occurs only in developing lymphocytes during the early stages of T and B cell maturation. It results in the highly diverse repertoire of antibodies/immunoglobulins and T cell receptors (TCRs) found in B cells and T cells, respectively.
The most common structural abnormality is the rearrangement of the T-cell receptor (TCR) gene. 95% of T-cell TCRs consist of an alpha and beta chain (encoded by TRA and TRB, respectively), while only 5% consist of gamma and delta chains (encoded by TRG and TRD, respectively). [4]
The RAG proteins initiate V(D)J recombination, which is essential for the maturation of pre-B and pre-T cells. Activated mature B cells also possess two other remarkable, RAG-independent phenomena of manipulating their own DNA: so-called class-switch recombination (AKA isotype switching) and somatic hypermutation (AKA affinity maturation). [ 2 ]
In 1983, Ellis Reinherz first defined the structure of the human T-cell receptor using anti-idiotypic monoclonal antibodies to T-cell clones, complemented by studies in the mouse by Philippa Marrack and John Kappler. [7] [8] Then, Tak Wah Mak [9] and Mark M. Davis [10] identified the cDNA clones encoding the human and mouse TCR respectively in ...
Generation of junctional diversity through recombination illustrated between two gene segments: D (blue) and J (green). Sections highlighted in red show nucleotides added at each stage. Junctional diversity describes the DNA sequence variations introduced by the improper joining of gene segments during the process of V(D)J recombination.
The most primitive T cells retain multipotential ability and can differentiate into cells of the myeloid or lymphoid lineages (B cells, DC, T cells, or NK cells). More differentiated double negative T cells (DN2 cells) have more limited potentiality but are not yet fully restricted to the T cell lineage (they can still develop into DC, T cells ...
Recombination signal sequences guide the enzyme complex to the V, D, and J gene segments that will undergo recombination during the formation of the heavy and light-chain variable regions in T-cell receptors and immunoglobulin molecules. [1]