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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.
T cells are one of the important types of white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface. T cells are born from hematopoietic stem cells, [1] found in the bone marrow.
1791 21673 Ensembl ENSG00000107447 ENSMUSG00000025014 UniProt P04053 P09838 RefSeq (mRNA) NM_001017520 NM_004088 NM_001043228 NM_009345 RefSeq (protein) NP_001017520 NP_004079 NP_001036693 NP_033371 Location (UCSC) Chr 10: 96.3 – 96.34 Mb Chr 19: 41.02 – 41.05 Mb PubMed search Wikidata View/Edit Human View/Edit Mouse Terminal deoxynucleotidyl transferase (TdT), also known as DNA ...
LAT was described in the early 1990s as a phosphoprotein of 36–38 kDa (pp. 36–38) rapidly phosphorylated on tyrosine residues following TCR ligation. [12] Cloning of the gene revealed that the protein product is a type III (leaderless) transmembrane protein of 262 aminoacids (long form) or 233 aminoacids (short form) in humans, 242 aminoacids in mouse, and 241 aminoacids in rat.
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 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]
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]
The purpose of thymocyte development is to produce mature T cells with a diverse array of functional T cell receptors, through the process of TCR gene rearrangement. Unlike most genes, which have a stable sequence in each cell which expresses them, the T cell receptor is made up of a series of alternative gene fragments.
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