Deletional rearrangement in the human T-cell receptor alpha-chain locus

Abstract

The antigen-specific receptor on the surface of mature T lymphocytes is a heterodimer consisting of polypeptides termed alpha and beta. In the course of characterizing human T-cell tumors with an immature (CD4-, CD8-) surface phenotype, we detected a 2-kilobase alpha-related transcript. Analysis of cDNA clones corresponding to this transcript established that a genetic element (which we call TEA, for "T early alpha") located between the alpha-chain variable- and joining-region genes had been spliced to the alpha constant region. The TEA transcript is present early in thymocyte ontogeny, and its expression declines during T-cell maturation. More important, the TEA area functions as an active site for rearrangement within the alpha gene locus. Blot hybridization of restriction enzyme-digested DNA with a TEA probe revealed a narrowly limited pattern of rearrangement in polyclonal thymic DNA, surprisingly different from the pattern expected for the mature alpha gene with its complex diversity. These DNA blots also showed that TEA is generally present in the germ-line configuration in cells expressing the gamma delta heterodimeric receptor and is deleted from mature (alpha beta-expressing) T-lymphocyte tumors and lines. Moreover, the TEA transcript lacked a long open reading frame for protein but instead possessed multiple copies of a repetitive element resembling those utilized in the heavy-chain class switch of the immunoglobulin genes. The temporal nature of the rearrangements and expression detected by TEA suggests that this recombination could mediate a transition between immature (gamma delta-expressing) T cells and mature (alpha beta-expressing) T cells.