As noted earlier, germ-line DNA encoding the T-cell receptor (TCR) undergoes V-(D)-J rearrangement to generate functional TCR genes. Rearrangement of both immunoglobulin and TCR germ-line DNA occurs by similar recombination processes mediated by RAG-1 and RAG-2 and involving recombination signal sequences with one-turn or two-turn spacers (see Figure 5-7). Despite the similarity of the processes, complete Ig-gene rearrangement of H and L chains occurs only in B cells and complete TCR-gene rearrangement is limited to T cells.
Hitoshi Sakano and coworkers have obtained results suggesting that a sequence within the K-chain 3' enhancer (3'KE) serves to regulate the joining of VK to JK in B and T cells. When a sequence known as the PU.1 binding site within the 3' K-chain enhancer was mutated, these researchers found that VK-JK joining occurred in T cells as well as B cells. They propose that binding of a protein expressed by T cells, but not B cells, to the unmutated K-chain enhancer normally prevents VK-JK joining in T cells. The identity of this DNA-binding protein in T cells remains to be determined. Similar processes may prevent rearrangement of heavy-chain and X-chain DNA in T cells.
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