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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.
[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 ...
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 ]
The ability of T cells to ignore healthy cells but respond when these same cells express a small number of foreign pMHCs is known as antigen discrimination. [20] [21] To do so, T cells have a very high degree of antigen specificity, despite the fact that the affinity to the peptide/MHC ligand is rather low in comparison to other receptor types ...
Each T cell's TCR is specific to one antigen and sits on the T cell's surface. The affinity of human TCRs to tumor antigens is relatively low, rendering them unable to recognize and kill tumor cells effectively. The modified T cell has much higher affinity, which enhances both recognition and affinity supporting the recognition of tumor cells. [1]
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.
Post-revision peripheral T cell repertoire is strengthening all essential features of self-tolerant and self-MHC-restricted T cell repertoire generated in the thymus while keeping all its hallmarks – reactivity towards foreign antigens and homeostatic proliferation in response to self-MHC, so-called tonic signaling.
Signal joint T-cell receptor excision circles (sjTRECs) might be used as a way to test the age of the individual from a blood sample. [2] The detection of sjTRECs can be further used as a diagnostic tool to monitor the thymic output (e.g., following hematopoietic stem cell transplantation or in cases of AIDS).