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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.
T cells are grouped into a series of subsets based on their function. CD4 and CD8 T cells are selected in the thymus, but undergo further differentiation in the periphery to specialized cells which have different functions. T cell subsets were initially defined by function, but also have associated gene or protein expression patterns.
Once mature, T cells emigrate from the thymus to provide vital functions in the immune system. [11] [12] Each T cell has a distinct T cell receptor, suited to a specific substance, called an antigen. [12] Most T cell receptors bind to the major histocompatibility complex on cells of the body.
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.
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 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 ]
Complementarity-determining regions (CDRs) are polypeptide segments of the variable chains in immunoglobulins (antibodies) and T cell receptors, generated by B-cells and T-cells respectively. CDRs are where these molecules bind to their specific antigen and their structure/sequence determines the binding activity of the respective antibody.