Antigen Specific Receptors of Lymphocytes

The ability of mature lymphoid cells to recognize a multitude of antigens, which constitutes a functional immune system, is mediated by a diversity of cell surface receptors, namely surface-bound Ig on B cells and the T-cell receptors (TCRs) on T cells. The specificity of antigen recognition is generated by rearrangements of separate Ig and TCR gene segments. Recombination events include a variable (V), a diversity (D) (in the case of Ig heavy chains and TCR-P and -8 chains), and a joining (J) gene segment, which encode the antigen-recognizing amino terminal part of antigen receptor chains. During the rearrangement process, nucleotides can be randomly deleted from the germline gene segments or inserted, probably through the activity of TdT polymerase, at the V-D and D-J junctions corresponding to the complementarity-determining region 3 (CDR3), which is of major importance in antigen recognition. Two recombination activation genes, RAG-1 and RAG-2, are absolutely essential for V(D)J joining both at the Ig and TCR loci. The junctional diversification of the genes creates a unique DNA sequence, which is specific for an individual lymphocyte and its progeny and therefore provides a clone-specific genetic marker, which is exploitable for the detection of monoclonality as well as for the monitoring of minimal residual disease in ALL.261-265

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