Q.15 The diversity in T-cell receptors is generated by
(A) gene rearrangements
(B) somatic hypermutation of rearranged V region
(C) gene conversion
(D) class switching
T-cell receptors (TCRs) achieve immense diversity primarily through gene rearrangements during T-cell development in the thymus. This process ensures the adaptive immune system recognizes a wide array of antigens presented by MHC molecules. The correct answer to the query is (A) gene rearrangements.
Correct Answer
Option (A) gene rearrangements is the primary mechanism generating TCR diversity. TCR genes (α, β, γ, δ chains) consist of V (variable), D (diversity, for β and δ), and J (joining) segments that undergo somatic V(D)J recombination. This randomly assembles functional genes, creating combinatorial diversity from germline segments, plus junctional diversity via nucleotide additions (N- and P-nucleotides) and exonucleases at junctions.
Option Explanations
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(A) Gene rearrangements: Enables >10^15 unique TCRs by mixing ~50 Vβ, ~2 Dβ, ~13 Jβ segments for β-chain, and similar for α-chain, focused on CDR3 for peptide-MHC contact. Junctional flexibility adds further variability, unlike fixed germline sequences.
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(B) Somatic hypermutation of rearranged V region: Occurs in B-cells to affinity-mature antibodies post-antigen exposure but absent in TCR genes, limiting TCR diversity to rearrangement only. TCRs avoid hypermutation to preserve self/non-self specificity.
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(C) Gene conversion: Generates diversity in immunoglobulin genes (e.g., chicken B-cells) or TCR γ/δ in some species, but not primary for mammalian αβ TCRs, which rely on V(D)J joining.
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(D) Class switching: Exclusive to B-cells, it changes antibody isotypes (e.g., IgM to IgG) via switch regions post-rearrangement, irrelevant to TCRs lacking constant region switching.
Key Processes
Gene rearrangements occur via RAG1/RAG2 enzymes cleaving DNA at recombination signal sequences (RSS), forming loops deleted or inverted, then ligated by NHEJ pathway. This ordered process (β before α) ensures productive pairs, with secondary rearrangements refining α-chains.
