Abnormal recombination products result from aberrant DNA rearrangement of the human T-cell antigen receptor beta-chain gene.

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Two unusual rearrangements of the T-cell antigen receptor beta-chain gene have occurred in the human T-cell tumor line CEM. The beta chain of the T-cell antigen receptor is encoded in germ-line DNA by immunoglobulin-like gene segments that rearrange during the somatic development of T cells to form active genes. Structural analysis of rearranged immunoglobulin genes has already revealed a great deal about the mechanisms by which these genes rearrange. To further characterize the mechanism by which beta-chain genes rearrange, we have determined the organization of the rearranged beta-chain gene segments in the human T-cell tumor line CEM. Three rearranged joining (J) or diversity (D) segments of the beta-chain gene are found in CEM. One of these segments rearranged during the formation of a normal rearranged beta-chain gene that comprises a variable (V beta), D beta, and J beta gene segment associated with a constant region gene segment. Two abnormal recombination products are found at the other rearranged beta-chain locus. One product has the structure, J beta-D beta-J beta, with the J beta gene segments joined in a head-to-head fashion, while the other one consists of a V beta-D beta recombined segment not associated with a J beta gene segment. We propose that the J beta-D beta-J beta structure was formed by an inversion of 6 kilobases of DNA and subsequently, a V beta-D beta rearrangement occurred. The presence of these products in CEM has important implications for our understanding of the mechanism by which somatic rearrangements of beta-chain gene segments occur.

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